|
| ||
|
|
||
Carboplatin
Selected AbstractsProspective non-randomized study of preoperative concurrent platinum plus 5-fluorouracil-based chemoradiotherapy with or without paclitaxel in esophageal cancer patients: long-term follow-upDISEASES OF THE ESOPHAGUS, Issue 2 2010M. Zemanova SUMMARY Combined modality treatment for esophageal carcinoma seems to improve survival over surgery alone. Different combinations of cytotoxic drugs have been studied to improve antitumor efficacy and limit the toxicity of chemoradiotherapy (CRT) with inconsistent results. We present a prospective study of neoadjuvant CRT with or without paclitaxel in chemotherapy schedule. One hundred seven patients (93 males, 14 females), median age 59 years (range 44,76), with operable esophageal cancer were enrolled. They received the following neoadjuvant therapy: Carboplatin, area under curve (AUC) = 6, intravenously on days 1 and 22, 5-fluorouracil (5-FU), 200 mg/m2/day, continuous infusion on days 1 to 42, radiation therapy 45 grays/25fractions/5 weeks beginning on day 1. Forty-four patients (41%) were furthermore non-randomly assigned to paclitaxel 200 mg/m2/3 h intravenously on days 1 and 22. Nutritional support from the beginning of the treatment was offered to all patients. Surgery was done within 4,8 weeks after completion of CRT, if feasible. All patients were evaluated for grade 3 plus 4 toxicities: leukopenia (28%), neutropenia (30%), anemia (6%), thrombocytopenia (31%), febrile neutropenia (6%), esophagitis (24%), nausea and vomiting (7%), pneumotoxicity (8%). Seventy-eight patients (73%) had surgery and 63 of them were completely resected. Twenty-two patients (20%) achieved pathological complete remission, and additional 20 (19%) had node-negative and esophageal wall-positive residual disease. There were 10 surgery-related deaths, mostly due to pulmonary insufficiency. Twenty-nine patients were not resected, 15 for early progression, 14 for medical reasons or patient refusal. After a median follow-up of 52 months (range 27,80), median survival of 18.0 months and 1-, 2-, 3- and 5-year survival of 56.7, 37.5, 27.0 and 21% was observed in the whole group of 107 patients. Addition of paclitaxel to carboplatin and continual infusion of FU significantly increased hematologic and non-hematologic toxicity, but treatment results as overall survival or time to progression did not differ significantly in groups with and without paclitaxel. Patients achieving pathological complete remission or nodes negativity after neoadjuvant therapy had favorable survival prognosis, whereas long-term prognosis of node positive patients was poor. Distant metastases prevailed as a cause of the treatment failure. Factors significant for survival prognosis in multivariate analysis were postoperative node negativity, performance status, and grade of dysphagia. Addition of paclitaxel to carboplatin and continual FU significantly increased hematologic and non-hematologic toxicity without influencing efficacy of the treatment. This study confirmed improved prognosis of patients after achieving negativity of nodes. Distant metastases prevailed as cause of the treatment failure. Prospectively, it is important to look for a therapeutic combination with better systemic effect. [source] Stage I seminoma: What should a practicing uro-oncologist do in 2009?INTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2009Julia Skliarenko Abstract Testicular tumors are uncommon, but they continue to represent an important group of malignancies in young men. It is the most common solid malignancy in males between the ages of 20 and 35, and primary germ cell tumors are the most common histological type. In the United States in 2008, approximately 4800 cases of seminoma, approximately 4100 of which were stage I disease were projected after the completion of staging investigations. Remarkable progress has been made in the treatment of testicular seminoma over the past 25 years. Management options of stage I seminoma include radiotherapy, surveillance, or adjuvant chemotherapy. Standard management until recent years has been adjuvant retroperitoneal radiotherapy. Although providing excellent long term results, this approach has been associated with increased risk of gonadal toxicity, development of secondary malignancies and an increased risk of cardiovascular disease. The use of surveillance in management of patients with stage I seminoma is therefore becoming more frequent as it minimizes the burden of treatment and maintains the cure rate at virtually 100%. Adjuvant chemotherapy using Carboplatin has been investigated as an alternative management approach. However, the long term outcomes of patients managed with Carboplatin are not yet clear and this strategy should only be used in a study setting. It has been suggested that more patients with stage I seminoma will die of their treatment than of their cancer; therefore, the thrust of modern management should be to maintain 100% cure while minimizing the burden of treatment. [source] Phase I Clinical Evaluation of Carboplatin in Tumor-Bearing Cats: A Veterinary Cooperative Oncology Group StudyJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2008W.C. Kisseberth Background: The dosage of carboplatin in cats has been reported anecdotally and experimentally in non-tumor-bearing cats, but the dosage for carboplatin treatment in tumor-bearing cats has yet to be defined in a prospective clinical trial. Purpose: To determine the maximally tolerated dose (MTD) and dose-limiting toxicosis (DLT) of carboplatin in tumor-bearing cats. Cats: Fifty-nine cats with measurable solid tumors. Methods: The starting dose of carboplatin was 160 mg/m2 of body surface area IV. Doses were increased by 20 mg/m2 in cohorts of 3,14 cats until the MTD was reached. Results: The 59 cats entered into this multi-institutional phase I study received 1 or more doses of carboplatin at various dosages and were evaluated for toxicity, response to treatment, or both. The MTD was 240 mg/m2 and neutropenia was the DLT. For the 1st cycle of treatment in 44 cats evaluated for neutropenia, 6 episodes of grade 3 or greater neutropenia occurred on days 7 (n=1), 14 (n=4), and 21 (n=1). There was no evidence of drug-induced nephrotoxicosis or pulmonary edema. Preliminary evidence of antitumor activity was observed in 7 of 59 (11.9%; 95% CI, 5.6,22.8%) cats evaluated for response to treatment. There was 1 complete response (cutaneous hemangiosarcoma) and 6 partial responses (4 injection site sarcomas, 1 oral squamous cell carcinoma, 1 lymphoma). Responses were of short duration (median, 42 days; range, 7,168 days). Conclusions and Clinical Importance: The dose of carboplatin recommended to treat tumor-bearing cats is 240 mg/m2 IV every 3,4 weeks. [source] Long-Term Results of a Phase III Randomized Trial of Postoperative Radiotherapy With or Without Carboplatin in Patients With High-Risk Head and Neck CancerTHE LARYNGOSCOPE, Issue 3 2008Athanassios Argiris MD Abstract Background: The role of postoperative radiotherapy and carboplatin in squamous cell carcinoma of the head and neck (SCCHN) has not been established. Methods: Patients with macroscopically resected stage III/IV SCCHN with high-risk pathologic features (,3 lymph nodes, extracapsular extension, perineural or angiolymphatic invasion, or involved margins) were randomized to receive postoperative radiotherapy alone (arm A) or the same radiotherapy plus carboplatin 100 mg/m2 intravenously once weekly during radiation (arm B). The primary endpoint was 2-year disease-free survival. Results: Seventy-six patients were randomized, of whom 72 were eligible and analyzable (36 in each arm). The study was prematurely closed because of slow accrual. With a median follow-up of 5.3 years, the disease-free survival at 2 and 5 years was 71% and 53% in arm B versus 58% (P = .27) and 49% (P = .72) in arm A. The overall survival at 2 and 5 years was 74% and 47% in arm B versus 51% (P = .04) and 41% (P = .61) in arm A. Serious toxicities were infrequent in both arms. Conclusions: We could not demonstrate a benefit with the addition of carboplatin to postoperative radiotherapy, possibly because of insufficient sample size. [source] Determination of carboplatin in canine plasma by high-performance liquid chromatographyBIOMEDICAL CHROMATOGRAPHY, Issue 8 2010Nicolas Villarino Abstract Carboplatin is an antineoplastic drug administered to treat different tumoral conditions in canine oncology. The objective of this study was to validate a high-performance chromatographic (HPLC) method which could be applied in canine pharmacokinetic studies. Following ultrafiltration using a Centrifree device, standards, quality controls and plasma samples were separated by isocratic reversed-phase HPLC on an Inertsil ODS-2 (250 × 4.6,mm i.d.) analytical column and quantified using UV detection at 220,nm. The mobile phase was potassium phosphate (pH 4.5), with a flow-rate of 1.0,mL/min. The procedure produced a linear curve (r2 > 0.999) over the concentration range 1,200,,g/mL. The lower limit of quantification was 1,,g/mL. The intra-assay and inter-assay precision was ,90%. The overall recovery was ,90%. The method was illustrated with a preliminary pharmacokinetic analysis on nine dogs treated with carboplatin at our hospital. Carboplatin disposition followed a monocompartmental structure in dogs and was characterized by a short half-life (50,min). Copyright © 2009 John Wiley & Sons, Ltd. [source] Carboplatin hypersensitivity reaction in pediatric patients with low-grade gliomaCANCER, Issue 4 2008A Canadian Pediatric Brain Tumor Consortium experience Abstract BACKGROUND. Carboplatin-based regimens have demonstrated activity in pediatric patients with low-grade glioma (LGG). However, carboplatin hypersensitivity reaction (Cb HSR) represents a common and limiting factor for the continuation of therapy. METHODS. The objectives of this study were to describe the prevalence, characteristics, and management of Cb HSR and to detail their impact on outcome. The authors conducted a comprehensive, national, retrospective review of children who were diagnosed with LGG between 1985 and 2004 and received treatment with carboplatin. RESULTS. One hundred five patients from 10 Canadian centers were included. The median patient age at diagnosis was 3.5 years (range, 0.3,16.8 years), and 33 patients (31.4%) had neurofibromatosis type 1. Carboplatin was administered monthly in 46 children and weekly in 59 children. Forty-four patients (41.9%) developed Cb HSR after a median of 10.5 infusions (range, 3,39 infusions). Cb HSR occurred significantly earlier among children on the weekly schedule (4.4 months vs 9.1 months; P = .02). The first allergic reaction was grade I or II in 36 patients (82%). The cumulative incidence of Cb HSR increased with the number of infusions, and there was no evidence of a plateau. The only predictive factor was being a girl rather than a boy (P = .02). Thirty-four of 44 patients with Cb HSR were re-exposed to carboplatin, and 24 of 34 patients (70.5%) had recurrent Cb HSR. A desensitization approach did not provide any advantage compared with premedication alone for altering Cb HSR. The median number of additional Cb infusions delivered was 4 (range, 0.5,34 infusions). The effect of Cb HSR on the 5-year progression-free survival rate was not statistically significant (P = .1). CONCLUSIONS. Forty-two percent of children with LGG who received carboplatin regimens experienced Cb HSR. Most rechallenged children had recurrent Cb HSR despite Cb HSR-altering regimens. Cb HSR did not have an impact on progression-free survival. Cancer 2008. © 2007 American Cancer Society. [source] Successful carboplatin desensitization in patients with proven carboplatin allergyCANCER, Issue 3 2005Ronit Confino-Cohen M.D. Abstract BACKGROUND Carboplatin is one of the most useful and well tolerated cytotoxic drugs for gynecologic malignancies. Hypersensitivity to carboplatin is not rare among patients receiving multiple recurrent treatments with this drug. The aim of the current study was to offer a safe and convenient carboplatin desensitization strategy to patients with a proven allergic reaction to this drug. METHODS Patients with an immediate objective allergic reaction to carboplatin were skin tested with the drug. A 6-hour carboplatin desensitization protocol was administered to the patients with a carboplatin-positive skin test on each of the following treatment courses. RESULTS Twenty-three patients with an allergic reaction to carboplatin and a positive skin test were included in the current study. Twenty patients (86.9%) were desensitized. One patient developed a mild urticarial rash. Nineteen patients tolerated 80 desensitization courses uneventfully. CONCLUSIONS The data presented a successful desensitization protocol for individuals with a proven allergic reaction to carboplatin. The protocol was safe and convenient and offered an effective therapeutic strategy to patients who required this drug. Cancer 2005. © 2005 American Cancer Society. [source] 4365: The role of transpupillary thermotherapy in combined treatment of retinoblastomaACTA OPHTHALMOLOGICA, Issue 2010SV SAAKYAN Purpose Retinoblastoma (RB) is one of the most serious ophthalmic pathology in childhood. Treatment options that provide eye preservation include chemotherapy, brachytherapy, external beam radiation, cryotherapy and laser treatment. The aim of our study is to evaluate efficiency of transpupillary thermotherapy (TTT) as a part of combined treatment of RB. Methods Our group consists of 30 RB patients (34 eyes). All patients received systemic chemotherapy (Carboplatin and Vincristine). Tumor thickness before TTT varied from 0.9 to 2.6 mm, tumor base diameter varied from 2 to 10 mm. Seven patients had monolateral RB, others had bilateral lesion. Five patients were treated with brachytherapy before TTT. TTT was performed using infrared diode laser Nidec DC 3300. Exposure time was 60 seconds. Width of laser beam was from 1000 to 2000 nm. TTT power setting varied from 600 to 900 mW. Eleven patients had TTT more then once. Follow-up period after TTT was up to 24 months. Results Control examination after TTT showed good response to the treatment in 27 eyes (79.4%). After TTT we saw hyperpigmented scar on the eye fundus at the place of previous tumor location, on OCT it looked like hyper-reflective stripe replacing all layers of a retina. Seven eyes (20.6%) were resistant to TTT, five of them were successfully treated by additional brachytherapy. Two eyes were enucleated because of uncontrolled tumor growth. Evaluation of metastatic disease in all patients revealed no signs of metastasis at the time of treatment or during follow-up. Conclusion TTT can be used in combined treatment of RB for small multifocal lesions. The method is rather simple and uncomplicated. Patients treated with TTT have better visual prognosis in comparison with brachytherapy. [source] Influence of Carbonate on the Binding of Carboplatin to DNACHEMISTRY & BIODIVERSITY, Issue 8 2008Robert Abstract The reaction of aged carboplatin (reaction of carboplatin in 24,mM NaHCO3 for 45,h, 37°, pH,8.6) with pBR322 DNA at 0 Prospective non-randomized study of preoperative concurrent platinum plus 5-fluorouracil-based chemoradiotherapy with or without paclitaxel in esophageal cancer patients: long-term follow-upDISEASES OF THE ESOPHAGUS, Issue 2 2010M. Zemanova SUMMARY Combined modality treatment for esophageal carcinoma seems to improve survival over surgery alone. Different combinations of cytotoxic drugs have been studied to improve antitumor efficacy and limit the toxicity of chemoradiotherapy (CRT) with inconsistent results. We present a prospective study of neoadjuvant CRT with or without paclitaxel in chemotherapy schedule. One hundred seven patients (93 males, 14 females), median age 59 years (range 44,76), with operable esophageal cancer were enrolled. They received the following neoadjuvant therapy: Carboplatin, area under curve (AUC) = 6, intravenously on days 1 and 22, 5-fluorouracil (5-FU), 200 mg/m2/day, continuous infusion on days 1 to 42, radiation therapy 45 grays/25fractions/5 weeks beginning on day 1. Forty-four patients (41%) were furthermore non-randomly assigned to paclitaxel 200 mg/m2/3 h intravenously on days 1 and 22. Nutritional support from the beginning of the treatment was offered to all patients. Surgery was done within 4,8 weeks after completion of CRT, if feasible. All patients were evaluated for grade 3 plus 4 toxicities: leukopenia (28%), neutropenia (30%), anemia (6%), thrombocytopenia (31%), febrile neutropenia (6%), esophagitis (24%), nausea and vomiting (7%), pneumotoxicity (8%). Seventy-eight patients (73%) had surgery and 63 of them were completely resected. Twenty-two patients (20%) achieved pathological complete remission, and additional 20 (19%) had node-negative and esophageal wall-positive residual disease. There were 10 surgery-related deaths, mostly due to pulmonary insufficiency. Twenty-nine patients were not resected, 15 for early progression, 14 for medical reasons or patient refusal. After a median follow-up of 52 months (range 27,80), median survival of 18.0 months and 1-, 2-, 3- and 5-year survival of 56.7, 37.5, 27.0 and 21% was observed in the whole group of 107 patients. Addition of paclitaxel to carboplatin and continual infusion of FU significantly increased hematologic and non-hematologic toxicity, but treatment results as overall survival or time to progression did not differ significantly in groups with and without paclitaxel. Patients achieving pathological complete remission or nodes negativity after neoadjuvant therapy had favorable survival prognosis, whereas long-term prognosis of node positive patients was poor. Distant metastases prevailed as a cause of the treatment failure. Factors significant for survival prognosis in multivariate analysis were postoperative node negativity, performance status, and grade of dysphagia. Addition of paclitaxel to carboplatin and continual FU significantly increased hematologic and non-hematologic toxicity without influencing efficacy of the treatment. This study confirmed improved prognosis of patients after achieving negativity of nodes. Distant metastases prevailed as cause of the treatment failure. Prospectively, it is important to look for a therapeutic combination with better systemic effect. [source] Selective dose escalation of chemoradiotherapy for locally advanced esophageal cancerDISEASES OF THE ESOPHAGUS, Issue 7 2008S. K. Seung SUMMARY., This phase II study assessed the use of concurrent continuous infusion of 5-fluorouracil and weekly carboplatin plus paclitaxel with selective radiation dose escalation for patients with localized esophageal cancer. Patients with esophageal carcinoma were staged by thoracic and abdominal computed tomography, endoscopic ultrasound, and positron emission tomography scans. Patients received a continuous infusion of 5-fluorouracil 225 mg/m2 on days 1 to 38 and intravenous paclitaxel 45 mg/m2 and carboplatin AUC 2 on days 1, 8, 15, 22, 29, and 36. Radiotherapy was delivered in 1.8-Gy fractions, 5 d/wk for 5.5 weeks. Six to 8 weeks after initial therapy, patients without metastatic progression but with a positive biopsy, or less than partial response received a 9-Gy boost with the same concurrent chemotherapy. Twenty-four patients were enrolled: 18 patients were enrolled initially; 6 additional patients were enrolled following a protocol amendment designed to reduce the esophagitis by adding the radioprotectant amifostine. Median follow-up was 30 months. Twenty (83%) patients had adenocarcinomas of the lower esophagus/gastroesophageal junction. Seventeen patients (81%) attained at least a partial response. Six patients received boost treatment. At 4 years, overall survival was 28%, cause-specific survival was 38%, locoregional control was 61%, and distant metastasis-free survival was 52%. Radiation delays ranged from 0 to 62 days (median, 8 d), primarily owing to esophagitis. In total, 28% of patients developed esophageal strictures requiring dilatations. There were no differences in esophageal strictures, local control, or survival with the addition of amifostine. [source] Gemcitabine induced digital ischaemia and necrosisEUROPEAN JOURNAL OF CANCER CARE, Issue 3 2010A. HOLSTEIN md HOLSTEIN A., BÄTGE R. & EGBERTS E.-H. (2010) European Journal of Cancer Care19, 408,409 Gemcitabine induced digital ischaemia and necrosis A 70-year-old woman presented with a 7-day history of severe pain, paresthesia, oedema, acrocyanosis and punctate haemorrhagic lesions on her fingertips. The complaints began 2 days after the second cycle of a first-line chemotherapy consisting of cisplatin or carboplatin, and gemcitabine due to advanced urothelial carcinoma. At the fingertips of both hands, haemorrhagic and partly ulcerative lesions were found; these were attributed to vascular toxicity of gemcitabine. Therapeutically sympathicolysis by bilateral blockade of the brachial plexus was performed, accompanied by intravenous administration of the prostacyclin analog iloprost, fractionated heparin subcutaneously and oral therapy with corticosteroids and aspirin. Digital amputation could be avoided. Acral ischemia is a rare but probably underreported adverse effect of gemcitabine therapy and a potential source of misdiagnosis. [source] Efficacy of tropisetron in patients with advanced non-small-cell lung cancer receiving adjuvant chemotherapy with carboplatin and taxanesEUROPEAN JOURNAL OF CANCER CARE, Issue 2 2008N. TSAVARIS md Even though significant progress has been made, chemotherapy-induced emesis remains a challenging problem. Few studies focus on emesis in patients treated with carboplatin and the observation period is limited to the initial 24 h following chemotherapy. Thus, we investigated if tropisetron (T) monotherapy can adequately prevent acute and delayed emesis in non-small-cell lung cancer (NSCLC) patients receiving a moderately emetogenic chemotherapy (MEC) (carboplatin-containing) regimen. Furthermore, we explored the merits of adding dexamethasone (D) or alprazolam (A) to T, especially in the setting of a pre-existing high level of stress. We studied 60 patients with advanced NSCLC receiving carboplatin and taxanes in three consecutive cycles. During the first cycle, patients received 5 mg of T intravenously before chemotherapy and the same dose per os on each of the following 3 days. In the second cycle, T was co-administered with 8 mg of D once a day, while, during the third cycle, T was combined with per os A 0.25 mg every 12 h and continued over the following 3 days. Finally, we evaluated the impact of stress on the anti-emetic response achieved with the previously described regimens. The combination of T + A was superior to T monotherapy and the combination of T + D, regarding the prevention of acute and delayed emesis. Both T + A and T + D combinations led to appetite improvement, while patients receiving T + A experienced sedation more frequently. Interestingly, subgroup analysis revealed that patients without underlying stress obtained no further benefit by the addition of A or D, while both T + A and T + D combinations led to a better anti-emetic response in patients with stress. In conclusion, T monotherapy provides a satisfactory result in controlling nausea and emesis caused by a MEC regimen in patients without stress. However, the addition of D and, mainly, A improves its anti-emetic effect in patients with obvious stress. [source] Synthesis of Polyamines from Ethylenediamine and Their Platinum(II) Complexes, Potential Antitumor AgentsEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 9 2006Mara Rubia Costa Couri Abstract This work describes the synthesis and characterization of five new amine ligands and also the preparation and characterization of their respective platinum(II) complexes by reaction with K2PtCl4 in water. These ligands were obtained by treatment of different halides or epoxides with ethylenediamine. Cytotoxic activity and cellular accumulation of three complexes were investigated in a human small-cell lung carcinoma cell line and its cisplatin resistant subline. The introduction of a spacer (cycle) between the two platinum atoms leads to a significant decrease in cytotoxic activity. At equitoxic doses, the intracellular platinum concentrations found for compounds 12 and 15 were significantly higher than those found for the reference compounds, cisplatin, carboplatin, or compound 9. This fact suggests that the formation of adducts between compounds 12 and 15 and the putative pharmacological target, DNA, is less favored. If these compounds bind more slowly to DNA, interaction with other intracellular ligands such as sulfur-containing molecules will become relevant and it may be the reason for the elevated intracellular platinum concentrations. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Synthesis of Novel gluco - and galacto -Functionalized Platinum Complexes,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 28 2009Janina Möker Abstract Cisplatin, carboplatin, oxaliplatin and further derivatives are worldwide established cytostatics for the treatment of a vast range of tumours. These drugs showed extraordinary success; however, side effects and primary or developed secondary resistance of tumour cells represent severe problems, which prompt the development of novel functionalized platinum complexes. Selectively protected monohydroxy derivatives of glucose and galactose could be etherified by ,-halo ethers. Further, Finkelstein reaction and malonate synthesis gave precursor glycoconjugates which were easily transformed into their (diammine)platinum complexes. First tests with different tumour cell lines show biological activity of the gluco -functionalized platinum complex.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Application of pharmacokinetic modelling to the routine therapeutic drug monitoring of anticancer drugsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2002Annick Rousseau Abstract Over the last 10 years, proofs of the clinical interest of therapeutic drug monitoring (TDM) of certain anticancer drugs have been established. Numerous studies have shown that TDM is an efficient tool for controlling the toxicity of therapeutic drugs, and a few trials have even demonstrated that it can improve their efficacy. This article critically reviews TDM tools based on pharmacokinetic modelling of anticancer drugs. The administered dose of anticancer drugs is sometimes adjusted individually using either a priori or a posteriori methods. The most frequent clinical application of a priori formulae concerns carboplatin and allows the computation of the first dose based on biometrical and biological data such as weight, age, gender, creatinine clearance and glomerular filtration rate. A posteriori methods use drug plasma concentrations to adjust the subsequent dose(s). Thus, nomograms allowing dose adjustment on the basis of blood concentration are routinely used for 5-fluorouracil given as long continuous infusions. Multilinear regression models have been developed, for example for etoposide, doxorubicin, carboplatin, cyclophosphamide and irinotecan, to predict a single exposure variable [such as area under concentration,time curve (AUC)] from a small number of plasma concentrations obtained at predetermined times after a standard dose. These models can only be applied by using the same dose and schedule as the original study. Bayesian estimation offers more flexibility in blood sampling times and, owing to its precision and to the amount of information provided, is the method of choice for ensuring that a given patient benefits from the desired systemic exposure. Unlike the other a posteriori methods, Bayesian estimation is based on population pharmacokinetic studies and can take into account the effects of different individual factors on the pharmacokinetics of the drug. Bayesian estimators have been used to determine maximum tolerated systemic exposure thresholds (e.g. for topotecan or teniposide) as well as for the routine monitoring of drugs characterized by a very high interindividual pharmacokinetic variability such as methotrexate or carboplatin. The development of these methods has contributed to improving cancer chemotherapy in terms of patient outcome and survival and should be pursued. [source] Concurrent chemoradiotherapy with weekly paclitaxel and carboplatin for locally advanced head and neck cancer: Long-term follow-up of a Brown University Oncology Group Phase II Study (HN-53)HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 3 2008Prakash B. Chougule MD Abstract Background. A phase II study was conducted using concurrent paclitaxel, carboplatin, and external beam radiotherapy (RT) in patients with advanced head and neck cancer. Methods. Forty-three patients (stage III, n = 12; stage IV, n = 31) were treated with 8 cycles of weekly paclitaxel (60 mg/m2), carboplatin (area under the curve [AUC] = 1), and RT (1.8 Gy daily; total dose, 66,72 Gy). Patients with initially palpable lymph nodes underwent neck dissection. Results. The overall clinical response rate was 91% (65% complete, 26% partial). Severe mucositis occurred in 37 (90%) patients, necessitating hospitalization in 13 (31%) patients. With a median follow-up of 49 months, the locoregional and distant failure rates were 26% and 21%, respectively. Conclusions. Concurrent paclitaxel, carboplatin, and RT for advanced head and neck cancer results in high complete response rates. Long-term follow-up has revealed the curative potential of this regimen, though the doses used resulted in unacceptable toxicity. © 2007 Wiley Periodicals, Inc. Head Neck 2008 [source] Response to paclitaxel and carboplatin in metastatic salivary gland cancer: A case report,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 4 2002Janet C. Ruzich DO Abstract Background Malignant tumors of the salivary gland are rare entities that are treated primarily by surgical resection. For patients with recurrent or unresectable disease, options include radiation therapy or chemotherapy; however, responses are few and of short duration. Patients with metastatic disease have been treated with chemotherapy, but, again, response rates have been low and of short duration. Methods A 52-year-old man was seen with a mass on his tongue. A biopsy revealed adenocarcinoma of a minor salivary gland. Ten months after surgical resection, neck dissection, and radiation therapy, the patient was found to have metastatic disease to the lung. Chemotherapy was initiated with carboplatin and paclitaxel. Results The patient obtained a complete response after six cycles of carboplatin and paclitaxel. Conclusions The use of carboplatin and paclitaxel in the setting of metastatic salivary gland cancer is a viable option. © 2002 Wiley Periodicals, Inc. Head Neck 24: 406,410, 2002 [source] Feasibility and long-term results of autologous PBSC transplantation in recurrent undifferentiated nasopharyngeal carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2001Mario Airoldi MD Abstract Background Recurrent undifferentiated nasopharyngeal carcinoma (UNPC) is a chemosensitive illness. Here we report long-term results of high-dose chemotherapy (HDC) as late intensification, with autologous peripheral blood stem cell (PBSC) support. Methods Six patients (5 men, 1 woman; median age 41years; median ECOG PS = 0) with recurrent UNPC (local, 2; local + nodal, 2; bone metastasis, 2) have been enrolled. All patients had been previously treated with neoadjuvant chemotherapy and radiotherapy; 3 of 4 local relapses had received a re-irradiation. Every patient received three courses of cisplatin + epirubicin and 1 cycle of epirubicin followed by PBSC collection. A median of 7.2 × 106/kg (range, 4.5,18) CD34+ cells were reinfused. HDC was according ICE scheme: ifosfamide, 2.5 g/m2/d, + carboplatin, 300 mg/m2/d, + VP-16, 300 mg/m2/d days 1 through 4. Results After conventional chemotherapy, we had 1 CR (16%), 3 PR (50%), and 2 NC (34%). After HDC, we had 4 CR (66%) ,1 PR (17%), and 1 MR (17%). Toxicity was manageable. After a median follow-up of 30 months (range, 14,50), two patients are alive without disease (34%), one is alive with bone disease (16%), and three (50%) died of disease at 16, 18, and 24 months. Conclusions HDC has an acceptable toxicity, can convert PR in CR, and seems effective, with long-lasting CRs. © 2001 John Wiley & Sons, Inc. Head Neck 23: 799,803, 2001. [source] Vorinostat increases carboplatin and paclitaxel activity in non-small cell lung cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 3 2010Taofeek K. Owonikoko Abstract We observed a 53% response rate in non-small cell lung cancer (NSCLC) patients treated with vorinostat plus paclitaxel/carboplatin in a Phase I trial. Studies were undertaken to investigate the mechanism (s) underlying this activity. Growth inhibition was assessed in NSCLC cells by MTT assay after 72 hr of continuous drug exposure. Vorinostat (1 ,M) inhibited growth by: 17% ± 7% in A549, 28% ± 6% in 128-88T, 39% ± 8% in Calu1 and 41% ± 7% in 201T cells. Vorinostat addition to carboplatin or paclitaxel led to significantly greater growth inhibition than chemotherapy alone in all 4 cell lines. Vorinostat (1 ,M) synergistically increased the growth inhibitory effects of carboplatin/paclitaxel in 128-88T cells. When colony formation was measured after drug withdrawal, vorinostat significantly increased the effects of carboplatin but not paclitaxel. The % colony formation was control 100%; 1 ,M vorinostat, 83% ± 10%; 5 ,M carboplatin, 41% ± 11%; carboplatin/vorinostat, 8% ± 4%; 2 nM paclitaxel, 53% ± 11%; paclitaxel/vorinostat, 46% ± 21%. In A549 and 128-88T, vorinostat potentiated carboplatin induction of gamma-H2AX (a DNA damage marker) and increased ,-tubulin acetylation (a marker for stabilized mictrotubules). In A549, combination of vorinostat with paclitaxel resulted in a synergistic increase in ,-tubulin acetylation, which reversed upon drug washout. We conclude that vorinostat interacts favorably with carboplatin and paclitaxel in NSCLC cells, which may explain the provocative response observed in our clinical trial. This likely involves a vorinostat-mediated irreversible increase in DNA damage in the case of carboplatin and a reversible increase in microtubule stability in the case of paclitaxel. [source] Anti-tumor efficacy of the nucleoside analog 1-(2-deoxy-2-fluoro-4-thio-,-D-arabinofuranosyl) cytosine (4,-thio-FAC) in human pancreatic and ovarian tumor xenograft modelsINTERNATIONAL JOURNAL OF CANCER, Issue 6 2005Deborah A. Zajchowski Abstract 1-(2-Deoxy-2-fluoro-4-thio-,- D -arabinofuranosyl) cytosine (4,-thio-FAC) is a deoxycytidine analog that has been shown previously to have impressive anti-proliferative and cytotoxic effects in vitro and in vivo toward colorectal and gastric tumors. In our present studies, the pharmacokinetic behavior in nude mice and the effectiveness of 4,-thio-FAC against human pancreatic and ovarian tumor growth were assessed in comparison with standard chemotherapeutic agents. Potent in vitro anti-proliferative effects were observed against pancreatic (Capan-1, MIA-PaCa-2, BxPC-3) and ovarian (SK-OV-3, OVCAR-3, ES-2) cancer cell lines with IC50 of 0.01,0.2 ,M. In vivo anti-tumor activity was evaluated in nude mice bearing subcutaneously (s.c.) implanted human pancreatic tumor xenografts or intraperitoneally (i.p.) disseminated human ovarian xenografted tumors. Oral daily administration of 4,-thio-FAC for 8,10 days significantly inhibited the growth of gemcitabine-resistant BxPC-3 pancreatic tumors and induced regression of gemcitabine-refractory Capan-1 tumors. 4,-Thio-FAC was also a highly effective inhibitor of ovarian peritoneal carcinomatosis. In the SK-OV-3 and ES-2 ovarian cancer models, 4,-thio-FAC prolonged survival to a greater extent than that observed with gemcitabine. Furthermore, the superiority of 4,-thio-FAC to carboplatin and paclitaxel was demonstrated in the ES-2 clear cell ovarian carcinoma model. Studies provide evidence that 4,-thio-FAC is a promising new alternative to gemcitabine and other chemotherapeutic drugs in the treatment of a variety of tumor indications, including pancreatic and ovarian carcinoma. © 2004 Wiley-Liss, Inc. [source] Solvent effect on the reactivity of CIS -platinum (II) complexes: A density functional approachINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 8 2008Pubalee Sarmah Abstract The structure and chemical reactivity of some selected cis -platinum(II) complexes, including clinically used drug molecules, cisplatin, carboplatin, and oxaliplatin are investigated using density functional theory (DFT) calculations. Calculated geometries of the complexes are in agreement with their available X-ray data. The global and local reactivity descriptors, such as hardness, chemical potential, electrophilicity index, Fukui function, and local philicity are calculated to investigate the usefulness of these descriptors for understanding the reactive nature and reactive sites of the complexes. Inclusion of solvent effect shows that both global and local descriptors change the trend of reactivity with respect to their trend in the gas phase. The stability of the complexes increases with the inclusion of water molecules. Simple regression analysis is applied to build up a quantitative structure-activity relationship (QSAR) model based on DFT derived electrophilicity index for the Pt(II) complexes against A2780 human ovarian adenocarcinoma cell line to establish the importance of the descriptor in predicting cytotoxicity. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2008 [source] Determination of binding sites in carboplatin-bound cytochrome c using electrospray ionization mass spectrometry and tandem mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 8 2005Gaosheng Yang Abstract Interaction of carboplatin with cytochrome c (Cyt. c) has been investigated by electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS). ESI-MS studies revealed that the ring-opened adducts of carboplatin with Cyt. c were formed in the stoichiometric ratio of 1 : 1 and 2 : 1 at pH 5.0 and 37 °C and in the stoichiometric ratio of 1 : 1 only at pH 7.0 and 37 °C. It was also found that Cyt. c could be cleaved by carboplatin at pH 2.5 and 50 °C. The cleaved fragments of Cyt. c were determined by ESI-MS and MS/MS analysis to be Glu66,Met80, Ac-Gly01,Met65, Glu66,Glu104, Ac-Gly01,Met80 and Ile81,Glu104. The carboplatin prefers to anchor to Met65 first, then to Met80. To further confirm the binding site of Met, AcMet-Gly was used as the model molecule to investigate its interaction with carboplatin and its hydrolysis reaction. On the basis of species detected during the reaction monitored by ESI-MS, a possible pathway of the cleavage reaction was proposed. Copyright © 2005 John Wiley & Sons, Ltd. [source] Third S. S. Ratnam Memorial Lecture 2007.JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 3 2009Ovarian cancer: Is there hope for women? Abstract Ovarian cancer is today the most lethal female cancer with an overall survival of only 49.9%. The currently available screening modalities are disappointing in detecting highly curable early stage ovarian cancer. Natural history of ovarian cancer is unknown; it appears it can develop quickly from normal looking ovaries. Timely referral of women with non-specific symptoms (such as abdominal bloating, pelvic pain) for an ultrasound scan or blood CA125 assessments may help in the early diagnosis. Patients with Stage IA or IB disease with grade 1 tumors have a cure rate of >90%; this is likely to be compromised by laparoscopic surgery. In selected patients fertility preservation with good obstetric outcome is possible. However, the relapse rate in ,high risk' early stage ovarian cancers is 40,45%; adjuvant chemotherapy is needed. Only 20,25% of those with stage III and IV disease are cured. Despite a high primary response (70%) majority (70,75%) will relapse and all are likely to succumb. Optimal debulking surgery followed by adjuvant chemotherapy are needed for stages III and IV disease; the outcome is superior if managed by gynecologic oncologists. Where cost of drugs is an important consideration, an alternative is carboplatin (an affordable and equally effective drug). The role of vaccines needs further study. When relapses occur palliation will be the aim in most instances. Oral contraceptives, breast feeding, tubal sterilization and hysterectomy also have a protective effect. Risk-reducing salpingo-oopherectomy has been suggested in women with BRCA mutations. [source] Primary adenocarcinoma of the vagina successfully treated with neoadjuvant chemotherapy consisting of paclitaxel and carboplatinJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 3 2009Shuji Takemoto Abstract Primary vaginal adenocarcinoma unassociated with antenatal diethylstilbestrol (DES) exposure is extremely rare. The strategy for treating this disease has not yet been established due to its rarity and, therefore, the prognosis remains poor. A 69-year-old woman presented with vaginal bleeding but no history of antenatal DES exposure. She had a solid tumor in the recto-vaginal space, diagnosed as FIGO stage III vaginal adenocarcinoma. After neoadjuvant chemotherapy consisting of paclitaxel and carboplatin, the tumor became undetectable. Thereafter, radiotherapy was applied to the pelvis and vagina in order to reinforce the state of remission. The patient remains free from recurrence 1 year after discharge. The present case was successfully treated with chemotherapy and radiotherapy, suggesting that chemotherapy may be an option for the treatment of this type of tumor. [source] Intermandibular malignant mesenchymoma in a crossbreed dogJOURNAL OF SMALL ANIMAL PRACTICE, Issue 9 2006S. Murphy A 12-year-old German shepherd crossbreed dog was presented with a submandibular mass that was initially diagnosed as myxosarcoma on incisional biopsy. Chest radiographs were taken for staging, and magnetic resonance imaging was performed to assess the feasibility of cytoreductive surgery before adjuvant radiotherapy. The dog underwent debulking surgery, and histology permitted reclassification of the tumour as a malignant mesenchymoma (with myxosarcomatous and osteosarcomatous differentiation). The dog was subsequently treated with four fractions of radiotherapy given at seven-day intervals and three doses of carboplatin. The dog remained stable following therapy until its condition acutely deteriorated, and it was euthanased 153 days after surgery. On postmortem examination, there were no signs of local tumour recurrence, but metastases were observed both in the thorax and in the abdomen. [source] Esophageal cancer: Outcomes of surgery, neoadjuvant chemotherapy, and three-dimension conformal radiotherapyJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2004FRCS(C), Éric Fréchette MD Abstract Neoadjuvant chemotherapy and radiation are being utilized with increasing frequency in the multimodal treatment of esophageal cancer, although their effects on morbidity, mortality, and survival remain unclear. The objective of this study was to determine the outcome of multimodal treatment in patients with localized esophageal cancer treated at a single institution. Between 1995 and 2002, 118 patients underwent treatment for localized esophageal cancer, utilizing surgery alone, chemoradiation alone, or surgery following neoadjuvant chemoradiation. There was no statistically significant difference in morbidity, mortality, or length of stay between the patients who received multimodal therapy when compared to surgery alone. A surgical resection after down-staging was possible in 9 out of 28 patients (32%) with a clinically non-resectable tumor (T4 or M1a). Forty-seven percent of the patients who received neoadjuvant therapy had a complete pathologic response with a 3-year survival of 59% as compared to only 20 months in those patients who did not achieve a complete response (P,=,0.037). Neoadjuvant chemotherapy administered concomitantly with conformal radiotherapy can be performed safely in the treatment of esophageal cancer, without increasing the operative morbidity, mortality, or length of stay. The higher complete response rates to neoadjuvant treatment (as compared to other reports) may be due to the use of three-dimensional conformal radiation therapy or the novel use of weekly carboplatin and paclitaxel. J. Surg. Oncol. 2004;87:68,74. © 2004 Wiley-Liss, Inc. [source] Tolerability of Gemcitabine and Carboplatin Doublet Therapy in Cats with CarcinomasJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2009I. Martinez-Ruzafa Background: This study was performed to determine the toxicity of gemcitabine-carboplatin doublet therapy in cats with carcinomas. Hypothesis: Gemcitabine and carboplatin are safe in tumor-bearing cats. Animals: Twenty cats with spontaneously occurring carcinomas. Methods: A cohort of 6 cats received gemcitabine (2 mg/kg IV) on days 1, 8, and 15 and carboplatin (10 mg/kg IV) immediately after gemcitabine on day 1 of a 21-day cycle. A 2nd cohort of 14 cats received carboplatin 4 hours after gemcitabine on day 1 and gemcitabine on day 8 but not day 15. The cycles were repeated every 21 days. Results: Cats in the 1st cohort received a median of 3.75 cycles per animal (range, 1,6). Two cats (33.3%) developed grade 3 or 4 neutropenia, 1 (16.7%) grade 4 thrombocytopenia, and 1 (16.7%) grade 3 gastrointestinal toxicity. Gemcitabine dose reductions and treatment delays occurred in 1 and 4 cats, respectively. Cats in the 2nd cohort received a median of 2 cycles per animal (range, 0.5,10). Two cats (14.3%) had grade 3 or 4 neutropenia and 1 (7.1%) had grade 3 and 4 gastrointestinal toxicity. One cat required gemcitabine dose reduction and 6 had treatment delays. In the 2nd cohort, of 11 cats with measurable tumors, there was 1 complete response (pancreatic carcinoma) and 1 partial response (squamous cell carcinoma, receiving concurrent nonsteroidal anti-inflammatory drugs). Conclusions and Clinical Importance: Gemcitabine-carboplatin combination appears moderately well tolerated in tumor-bearing cats. Minimal patient benefit suggests that alternative schedules or combinations of gemcitabine with other agents should be explored. [source] Phase I Clinical Evaluation of Carboplatin in Tumor-Bearing Cats: A Veterinary Cooperative Oncology Group StudyJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2008W.C. Kisseberth Background: The dosage of carboplatin in cats has been reported anecdotally and experimentally in non-tumor-bearing cats, but the dosage for carboplatin treatment in tumor-bearing cats has yet to be defined in a prospective clinical trial. Purpose: To determine the maximally tolerated dose (MTD) and dose-limiting toxicosis (DLT) of carboplatin in tumor-bearing cats. Cats: Fifty-nine cats with measurable solid tumors. Methods: The starting dose of carboplatin was 160 mg/m2 of body surface area IV. Doses were increased by 20 mg/m2 in cohorts of 3,14 cats until the MTD was reached. Results: The 59 cats entered into this multi-institutional phase I study received 1 or more doses of carboplatin at various dosages and were evaluated for toxicity, response to treatment, or both. The MTD was 240 mg/m2 and neutropenia was the DLT. For the 1st cycle of treatment in 44 cats evaluated for neutropenia, 6 episodes of grade 3 or greater neutropenia occurred on days 7 (n=1), 14 (n=4), and 21 (n=1). There was no evidence of drug-induced nephrotoxicosis or pulmonary edema. Preliminary evidence of antitumor activity was observed in 7 of 59 (11.9%; 95% CI, 5.6,22.8%) cats evaluated for response to treatment. There was 1 complete response (cutaneous hemangiosarcoma) and 6 partial responses (4 injection site sarcomas, 1 oral squamous cell carcinoma, 1 lymphoma). Responses were of short duration (median, 42 days; range, 7,168 days). Conclusions and Clinical Importance: The dose of carboplatin recommended to treat tumor-bearing cats is 240 mg/m2 IV every 3,4 weeks. [source] Treatment of Dogs with Oral Melanoma by Hypofractionated Radiation Therapy and Platinum-Based Chemotherapy (1987,1997)JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2003Kim P. Freeman This retrospective study in 39 dogs with incompletely resected oral melanoma examined the efficacy of hypofractionated radiation therapy and platinum-containing chemotherapy. All dogs were completely staged, with the majority of dogs classified as stage I. Dogs received 6 weekly fractions of 6-gray (Gy) megavoltage irradiation with a cobalt-60 unit or a 4-MeV (megaelectron volts) linear accelerator. Dogs received cisplatin (10,30 mg/m2 IV) or carboplatin (90 mg/m2 IV) chemotherapy 60 minutes before radiation delivery. Durations of local control, metastasis-free survival time, and overall survival time were recorded. By the Kaplan-Meier method, 15% of the dogs had local recurrence within a median time of 139 days. Fifty-one percent of the dogs developed metastatic disease within a median time of 311 days (range, 24,2,163 days). Median survival time for all 39 dogs was 363 days. The combined use of chemotherapy and radiation therapy in this protocol provided local control consistent with previous studies. Low-dose chemotherapy was used with the intent of enhancing radiation therapy for the local control of an incompletely excised tumor. Survival times were longer than previously reported for dogs with oral malignant melanoma. Additional studies are required to determine whether these results were due to the effects of chemotherapy on microscopic disease or the enhanced local control provided by chemoradiation therapy. [source]
| | ||||||||||||||||||||||||||||||