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Febrile Neutropenia (febrile + neutropenia)
Selected AbstractsDeveloping anticancer chemotherapy services in a developing country: Hodgkin lymphoma experiencePEDIATRIC BLOOD & CANCER, Issue 4 2008Jagdish Chandra MD Abstract Background and Objective Reporting on how the cancer treatment facilities were developed at a medical college hospital in India and the profile and outcome of patients with Hodgkin lymphoma (HL) at this new center were the objectives of the study. Methods Patients under 18 years with a diagnosis of HL were evaluated using abdominal ultrasonography, CT scan examination of chest, abdomen and pelvis and bone marrow examination. Most patients were treated with combination chemotherapy. Departments of Radiodiagnosis and Pathology were involved for evaluation. Radiotherapy when required was made available at a nearby hospital. Results Thirty-five patients between 1.2 and 18 years (median age 7 years) were diagnosed as HL during the study period. Advanced disease (Stage IIb or more) was present in 83% cases. Mixed cellularity was the commonest histological subtype (50.5%). Primary therapy used was COPP in 29 (83%) cases. Of the 34 patients who received treatment 30 showed initial good response to therapy. One patient responded to ABVD after having progression on COPP. Of 31 responders, 4 relapsed. Twenty-seven patients (80%) are surviving free of disease for a median follow up of 4.5 years (range 1.5,18 years). Chemotherapy was well tolerated. Febrile neutropenia occurred in four cases. Conclusions Pediatric HL in India was characterized by advanced disease at presentation. Mixed-cellularity was the predominant histological subtype. An effective program was developed with initial attention to patients with HL. Pediatr Blood Cancer 2008;51:485,488. © 2008 Wiley-Liss, Inc. [source] 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] Once-per-cycle pegfilgrastim in breast cancer patients treated with docetaxel/epidoxorubicin/cyclophosphamideEUROPEAN JOURNAL OF CANCER CARE, Issue 2 2010L. MONTELLA md MONTELLA L., ADDEO R., GUARRASI R., CENNAMO G., FAIOLA V., CAPASSO E., CARAGLIA M. & DEL PRETE S. (2010) European Journal of Cancer Care19, 200,204 Once-per-cycle pegfilgrastim in breast cancer patients treated with docetaxel/epidoxorubicin/cyclophosphamide The incidence of neutropenia following combination chemotherapy is significant in breast cancer and impairs patients' quality of life. Colony-stimulating factors significantly decrease the risk of febrile neutropenia (FN). Aim of the present study was to assess the efficacy and safety profile of once-per-cycle pegfilgrastim in reducing FN in breast cancer patients treated with docetaxel (75 mg/m2), epidoxorubicin (75 mg/m2), cyclophosphamide (500 mg/m2) administered every 3 weeks. Thirty-five breast cancer patients were enrolled. Chemotherapy was administered in adjuvant, neoadjuvant and metastatic setting respectively in 26, 4 and 5 patients. Toxicity was monitored with programmed clinical evaluation and blood sampling. All patients completed the therapeutic programme consisting of six cycles for overall 210 cycles. The FN appeared in 6 out of 35 patients (17%), requiring dose reduction in 3 patients. Hypertransaminasemia was registered in two patients. In one patient pegfilgrastim administration was stopped because of skin hypersensititivity reaction. In conclusion, pegfilgrastim was able to maintain doses and timing of docetaxel/epidoxorubicin/cyclophosphamide in almost all breast cancer patients treated in this series. The reduced need for daily administration of colony-stimulating factors, blood sampling, antibiotic therapy and hospitalization has a significant impact in terms of both quality of life and pharmaco-economic evaluations. [source] Human immunodeficiency virus-associated diffuse non-Hodgkin's lymphoma in Venezuelan patients: treatment with full-dose cyclophosphamide-doxorubicin-vincristine-prednisone without routine use of granulocyte-colony stimulating factorEUROPEAN JOURNAL OF CANCER CARE, Issue 5 2006D.E. HERNĄNDEZ md, phd The routine use of granulocyte-colony stimulating factor (G-CSF) for 10 days during full-dose cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) chemotherapy in HIV-associated diffuse non-Hodgkin's lymphoma (NHL) patients is very expensive in developing countries. We treated 22 HIV-associated diffuse NHL patients with standard-dose CHOP and used G-CSF after an episode of febrile neutropenia until neutrophil count reached 1000/mm3. The clinical response was: complete response (36%), partial response (32%), stable disease (14%) and progression (18%). There were no toxicity-related deaths. Grade 3 or 4 neutropenia was observed in 16% of cycles, but only 8% were complicated with febrile neutropenia. Seventeen patients died (median survival 15 months; range 2,70). There are five patients alive (median survival 24+ months; range 17,36+). Our experience showed that we can treat HIV-related NHL patients with full-dose CHOP, achieve good responses and have an acceptable toxicity profile, with the use of G-CSF as needed. [source] Japanese guidelines for prevention of perioperative infections in urological fieldINTERNATIONAL JOURNAL OF UROLOGY, Issue 10 2007Tetsuro Matsumoto Abstract: For urologists, it is very important to master surgical indications and surgical techniques. On the other hand, the knowledge of the prevention of perioperative infections and the improvement of surgical techniques should always be considered. Although the prevention of perioperative infections in each surgical field is a very important issue, the evidence and the number of guidelines are limited. Among them, the preparation of guidelines has progressed, especially in gastrointestinal surgery. The Center for Disease Control and Prevention (CDC) proposed guidelines for the prevention of surgical site infections, which have been used worldwide. In urology, the original guidelines were different from those of general surgery, due to many endourological procedures and urine exposure in the surgical field. The Japanese Society of UTI Cooperative Study Group has thus framed these guidelines supported by The Japanese Urological Association. The guidelines consist of the following nine techniques: open surgeries, laparoscopic surgeries, transurethral resection of bladder tumor, ureterorenoscope and transurethral lithotripsy, transurethral resection of the prostate, prostate biopsy, cystourethroscope, pediatric surgeries in the urological field, and extracorporeal shock wave lithotripsy and febrile neutropenia. These are the first guidelines for the prevention of perioperative infections in the urological field in Japan. Although most of these guidelines were made using reliable evidence, there are parts without enough evidence. Therefore, if new reliable data is reported, it will be necessary for these guidelines to be revised in the future. [source] Phase I,II trial of weekly gemcitabine plus high-dose 5-fluorouracil and leucovorin in advanced pancreatic cancerJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2006HER-SHYONG SHIAH Abstract Background:, Pancreatic cancer is a dismal disease. Few drugs, including gemcitabine and 5-fluorouracil (5-FU), have notable antitumor effects against advanced pancreatic cancer. The purpose of the present study was to determine the maximum tolerated dose (MTD) of 5-FU and the efficacy and toxicity profile of weekly gemcitabine plus infusional 5-FU/leucovorin in advanced pancreatic cancer. Methods:, Patients with histo-/cytologically confirmed, advanced pancreatic cancer were eligible. Treatment consisted of a 30-min infusion of gemcitabine (800 mg/m2), followed by a 24-h infusion of 5-FU and leucovorin (300 mg/m2) at day 1, day 8 and day 15 every 28 days, and was termed the GemFL24 regimen. The dose of 5-FU was escalated from 1600, 2000, to 2600 mg/m2 in the phase I study, and fixed MTD for subsequent enrolled patients. Results:, Eighteen patients were enrolled in the phase I study, and 24 in phase II. The MTD of 5-FU was 2000 mg/m2, with major dose-limiting toxicities being febrile neutropenia and delayed recovery from neutropenia. The dose intensity of gemcitabine of the 35 patients with 5-FU dosage set at MTD was 593 mg/m2 per week. In the entire series of 42 patients, myelosuppression was the main toxicity, with grade 3 neutropenia in eight patients, and grade 3/4 thrombocytopenia in six. On an intention-to-treat analysis, the overall and clinical benefit response rates were 22% and 46%, respectively; with median progression-free and overall survival of 4.1 and 6.9 months, respectively. Conclusions:, The GemFL24 regimen is a feasible and moderately active treatment with manageable toxicities for advanced pancreatic cancer, and could be a basis for further combination with other anticancer drugs. [source] Malnutrition and neutropenia in children treated for Burkitt lymphoma in MalawiPEDIATRIC BLOOD & CANCER, Issue 1 2009Trijn Israėls MD Abstract Background Infection in neutropenic children is a major cause of morbidity and mortality in children treated for cancer. In developing countries, children with cancer are often malnourished at diagnosis. In Blantyre, Malawi, children with Burkitt lymphoma are treated with a local protocol with limited toxicity. The aim of this study was to evaluate the incidence and outcome of febrile neutropenia during this treatment and the association with malnutrition at diagnosis. Methods We documented nutritional status, febrile and/or neutropenic episodes, antibiotic therapy and short term outcome of all children with Burkitt lymphoma treated according to the local protocol and admitted from January 2007 to March 2008. Results Fifty eight (69%) of 84 patients were acutely malnourished at diagnosis with an arm muscle area (AMA) below the 5th percentile. Malnutrition at diagnosis was associated with a significantly higher rate of profound neutropenia. This association remained significant (OR 12; 95% C.I. 1.5 - infinitely; P,=,0.012) after control for clinical stage of disease, bone marrow involvement and HIV infection which are possible confounders. All patients with profound neutropenia, prolonged neutropenia and treatment related deaths were malnourished at diagnosis. Four (4.9%) of 81 patients died of treatment related causes; three of them due to a Gram negative septicaemia. Conclusion Acute malnutrition at diagnosis is associated with significantly more treatment related profound neutropenia. The intensity of chemotherapeutic regimens has to be adapted to the level of available supportive care and patients' nutritional status and tolerance to avoid unacceptable morbidity and mortality. This local treatment protocol for Burkitt lymphoma has a treatment related mortality of 5% in patients in Malawi. Pediatr Blood Cancer 2009;53:47,52. © 2009 Wiley-Liss, Inc. [source] Are we finally ready for outpatient management of febrile neutropenia?PEDIATRIC BLOOD & CANCER, Issue 6 2007Shermini Saini MD No abstract is available for this article. [source] Outcome of children with B cell lymphoma in Venezuela with the LMB-89 protocolPEDIATRIC BLOOD & CANCER, Issue 5 2004G. Acquatella MD Abstract Background We analyzed the results of the LMB-89 protocol performed in seven centers in Venezuela in 96 children having B-cell non-Hodgkin lymphoma treated from 1995 to 2002. Procedure Mean age was 7.1 years with 71 (74%) been male. Eighty-two patients (85%) had diffuse small cell lymphoma Burkitt and Burkitt-like, and 14 (15%) had diffuse large B-cell lymphoma. Initial disease sites included the abdomen in 67%, peripheral nodes in 8%, and mediastinal in 4%. Treatment was directed to risk groups as described for LMB-89 protocol. Group A: seven patients (7%), group B: 80 patients (83%), and group C: nine patients (9%). Results Mean follow-up was 35,±,31 months. Complete remission (CR) occurred in 70 patients (73%); four patients (6%) had relapse during the first year and ten patients (10%) had progressive disease. Overall survival (OS) and event free survival (EFS) were 85 and 80% at 1 year, and 82 and 75% at 2 years, respectively. The EFS by therapeutic groups at 3 years was A: 100%; B: 76%, and C: 56%. Toxicity: neutropenia in 75%, thrombocytopenia in 63%, febrile neutropenia in 39%. Viral infections: hepatitis B in 20%, hepatitis C in 2%, and Herpes zoster in 3%. Tumor lysis syndrome (TLS) occurred in 9% during induction phase with a high mortality of 44% (urate-oxidase was available only at the end of the study). Conclusions The high mortality rate during induction phase prohibited a better EFS. Prophylactic use of xantine-oxidase may improve future results. The high incidence of hepatitis B requires a vaccination program. © 2004 Wiley-Liss, Inc. [source] Evolving concepts of management of febrile neutropenia in children with cancerPEDIATRIC BLOOD & CANCER, Issue 2 2002Elmar Orudjev MD Abstract Background Recent investigations of febrile neutropenia in pediatric cancer patients have identified subsets of low-risk patients who can be managed with less antibiotic therapy than previously recommended standards. Methods and Materials PubMed and Medline were searched for prospective trials and reviews of febrile neutropenia in children. Magnitude and duration of fever and neutropenia, comorbidities, and therapeutic strategies were examined. Results Twenty-seven prospective trials and five reviews were identified. The child with cancer and low-risk febrile neutropenia is clinically well and afebrile within 24,96 hr of antibiotic therapy and has evidence of marrow recovery with a rising phagocyte count. Disqualifying comorbidities include leukemia at diagnosis or in relapse, uncontrolled cancer, age under 1 year, medical condition(s) that would otherwise require hospitalization and social or economic conditions that may potentially compromise access to care or compliance. Therapeutic strategies include parenteral or oral antibiotics in the hospital with early discharge or parenteral antibiotics in the outpatient setting followed by oral or parenteral therapy and daily reassessment. Although as many as 25% of low-risk patients require modification of therapy and/or hospitalization, life-threatening or fatal infection is exceptional. Conclusion One-third to one-half the children with febrile neutropenia are at low-risk of serious infection. In the context of clinic trials, they can be safely managed with inpatient or outpatient strategies that maintain close follow-up and reduce the burden of antibiotic therapy. Adoption of these alternative strategies as the standard of care should proceed with caution guided by written protocols. Med Pediatr Oncol 2002;39:77,85. © 2002 Wiley-Liss, Inc. [source] Predictors of Toxicity and Toxicity Profile of Adjuvant Chemotherapy in Elderly Breast Cancer PatientsTHE BREAST JOURNAL, Issue 4 2009Praveen Garg MD Abstract:, Women older than 70 years have been underrepresented in breast cancer adjuvant chemotherapy trials due to concerns about toxicity, safety and tolerance of chemotherapy. The aim of our study was to assess the tolerance of chemotherapy in older women with breast cancer and determine patterns of toxicity including the impact of age, chemotherapy regimen, functional status and comorbid conditions on this toxicity. We retrospectively reviewed the charts of early stage (stages 1 and 2) breast cancer patients older than 70 years from 1998 to 2004. A total of 62 patients, with mean age of 74.3 years, were identified. Chemotherapy was completed in 89% patients. Overall 79% completed chemotherapy without any significant side-effects, dose reductions, or breaks during chemotherapy. Using logistic regression model increasing age was not associated with early termination of chemotherapy (p = 0.19, OR: 0.868, 95% CI: 0.7,1.076). However, increasing age, lower functional status, and higher comorbidity index scores were associated with reduction in dose and breaks in chemotherapy. None of the patients who received pegfilgrastim prophylactically developed high-grade neutropenia. Our study suggests that adjuvant chemotherapy is safe in elderly patients. Older patients with good functional status and low comorbidity index scores tolerate chemotherapy as well as the younger patients. Prophylactic use of pegfilgrastim may reduce occurrence of severe neutropenia and related toxicity such as febrile neutropenia in the elderly patient. [source] Granulocyte Colony-stimulating Factor Suppresses Autologous Tumor Killing Activity of the Peripheral Blood Lymphocytes in the Patients with Ovarian CarcinomaAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2004Yoshiaki Ohta Problem:, Granulocyte colony-stimulating factor (G-CSF) is often administered to patients with chemotherapy-induced leukocytopenia. However, adequate attention has not been paid to its effects on cancer immunology. Reported by us and others, G-CSF often induces immunosuppression and down-regulation of response T helper (Th)2 directed immune reaction both in vivo and in vitro. In this study, we analyzed the effects of G-CSF on interferon (IFN)- , production and autologous tumor killing (ATK) activities of peripheral blood mononuclear cells (PBMCs). Methods of study:, In order to evaluate the cytokine-induced activation of peripheral T and natural killer (NK) cells, we analyzed IFN- , production by interleukin (IL)-2- and IL-12-stimulated PBMCs, using the ELISPOT assay. Specific killing of autologous tumor cells was evaluated by lactate dehydrogenase (LDH) release assay. Results:, The PBMC collected from both cancer-bearing patients and healthy subjects showed IL-2- and/or IL-12-induced IFN- , production. The frequency of IFN- , producing cells was significantly higher in the normal subjects compared with the patients with advanced ovarian carcinoma. The ATK activity was also enhanced in IL-2- and/or IL-12-stimulated PBMCs of patients with ovarian carcinoma. G-CSF almost completely abolished IFN- , production and ATK activity of PBMC stimulated with IL-2 and/or IL-12. Conclusions:, The G-CSF appears to be a suppressor of antitumor immunity. Routine administration of G-CSF to cancer patients may not be recommended, except for febrile neutropenia. [source] Toxicity of docetaxel plus cyclophosphamide as adjuvant therapy for breast cancer in Chinese patients , the Hong Kong experienceASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 2 2009Tsz-Kok YAU Abstract Aims: The docetaxel and cyclophosphamide (TC) regimen is increasingly popular as adjuvant chemotherapy for operable breast cancers. We conducted a retrospective study in Hong Kong to evaluate the toxicity of this regimen in Chinese patients. Methods: Between January 2007 and May 2008 76 female Chinese patients with resected stage I,III operated invasive breast cancer were treated with 4 cycles of TC (75 and 600 mg/m2, respectively, administered i.v. every 3 weeks for four cycles) in two public regional cancer centers of Hong Kong. A total of 24 (32%) patients also received primary prophylactic ciprofloxacin (500 mg twice daily, day 5,14). Chemotherapy-related toxicities were graded by the CTCAE version 3.0. Results: The median age was 50 (range 26,67). A total of 68 (89%) patients successfully completed four cycles of chemotherapy. 72 (95%) and 16 (21%) patients developed grade 3,4 neutropenia and febrile neutropenia (FN) infection, respectively, in one or more cycles. However, no grade 3,4 anemia or thrombocytopenia events were observed. Other grade 3,4 non-hematological toxicities were also uncommon, apart from allergic reactions in two (3%) patients. No viral reactivation was observed among the 8 hepatitis B carriers. Patients with prophylactic ciprofloxacin had less grade 3,4 FN infection (13% vs 25%, P = 0.214) and a higher chance of receiving the full scheduled dose (88% vs 62%, P = 0.045) than patients without. Conclusion: The myelotoxicity of TC was substantially higher in Chinese patients compared with non-Chinese patients in developed countries. Routine prophylactic measures are recommended to maintain the dose levels and reduce the risk of FN. [source] Phase II study of gemcitabine and docetaxel in combination for the treatment of metastatic breast cancerASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2009Shom GOEL Abstract Aim: Gemcitabine (G) and docetaxel (D) have both shown activity in the treatment of anthracycline-pretreated patients with metastatic breast cancer. This phase II study was designed to evaluate the safety and efficacy of the GD combination. Methods: Patients with measurable locally advanced or metastatic breast cancer who had previously received anthracycline-based therapy were eligible. The patients received D 40 mg/m2 followed by G 800 mg/m2 IV on days 1 and 8 every 3 weeks for a maximum of eight cycles. Results: Thirty patients were enrolled and received a median of five cycles (range 0,8). Of these, 24 were evaluable for efficacy, with an overall response rate of 29.2% (95% CI, 12.6,51.1%). An additional 36.7% had a stable disease for an overall clinical benefit of 65.9%. The median duration of response was 2.1 months (95% CI, 2.0,3.6 months) and the median time to disease progression was 5.5 months (95% CI, 2.0,8.9 months). The median survival time was 16.7 months (95% CI, 7.3,32.0 months). Myelosuppression was the major toxicity, with grade 3/4 neutropenia in 73.3% of patients and febrile neutropenia in 6.7%. Conclusion: Weekly G and D is an active and safe regimen in treating metastatic breast cancer. The response rate was lower than that previously reported for this combination, which may relate to the lower doses used and the weekly D schedule. It may be worthwhile to further explore this combination to determine the optimal dosing schedule. [source] Prospective screening by a panfungal polymerase chain reaction assay in patients at risk for fungal infections: implications for the management of febrile neutropeniaBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2000Holger Hebart Invasive fungal infections are a major cause of mortality in neutropenic cancer patients. To determine whether a polymerase chain reaction (PCR)-based assay enabled the identification of patients at risk for invasive fungal infections, a prospective monitoring once per week was performed during 92 neutropenic episodes in patients receiving chemotherapy for acute leukaemia or high-dose therapy followed by allogeneic or autologous stem cell transplantation, with the investigators blinded to clinical and microbiological data. PCR positivity was documented in 34 out of 92 risk episodes. All patients developing proven invasive fungal infection were found PCR positive, and PCR was found to be the earliest indicator of invasive fungal infection preceding clinical evidence by a mean of 5·75 d (range 0,14 d). In febrile neutropenic patients without a prior history of invasive fungal infection, a sensitivity of 100% and a specificity of 73% of the PCR assay for the development of proven or probable invasive fungal infection was documented. In conclusion, panfungal PCR performed prospectively once a week enabled the identification of patients at high risk for invasive fungal infections. [source] Phase 1 trial of temozolomide plus irinotecan plus O6 -benzylguanine in adults with recurrent malignant gliomaCANCER, Issue 13 2009Jennifer A. Quinn MD Abstract BACKGROUND: The current study was a phase 1 clinical trial conducted with patients who had recurrent or progressive malignant glioma (MG). The trial was designed to determine the maximum tolerated dose (MTD) and toxicity of irinotecan (CPT-11) when administered with temozolomide (TMZ) and O6 -benzylguanine (O6 -BG). METHODS: All 3 drugs, CPT-11, TMZ, and O6 -BG, were administered on Day 1 of a 21-day treatment. First, patients were treated with a 1-hour bolus infusion of O6 -BG at a dose of 120 mg/m2 followed immediately by a 48-hour continuous infusion of O6 -BG at a dose of 30 mg/m2/d. Second, within 60 minutes of the end of the 1-hour bolus infusion of O6 -BG, TMZ was administered orally at a dose of 355 mg/m2. Third, 1 hour after administration of TMZ, CPT-11 was infused over 90 minutes. Patients were accrued to 1 of 2 strata based on CYP3A1- and CYP3A4-inducing antiepileptic drug (EIAED) use; dose escalation was conducted independently within these strata. RESULTS: Fifty-five patients were enrolled. In both strata, the dose-limiting toxicities were hematologic and included grade 4 neutropenia, febrile neutropenia, leukopenia, and/or thrombocytopenia. For Stratum 1 (EIAEDs), when TMZ was administered at a dose of 355 mg/m2, the MTD of CPT-11 was determined to be 120 mg/m2. In contrast, for Stratum 2 (no EIAEDs), when TMZ was administered at a dose of 200 mg/m2, the MTD of CPT-11 was determined to be 80 mg/m2. CONCLUSIONS: The authors believe that the results of the current study provide the foundation for a phase 2 trial of O6 -BG in combination with CPT-11 and TMZ in patients with MG. Cancer 2009. © 2009 American Cancer Society. [source] Randomized phase 2 study of subcutaneous amifostine versus epoetin-, given 3 times weekly during concurrent chemotherapy and hyperfractionated radiotherapy for limited-disease small cell lung cancerCANCER, Issue 7 2008Hye-Suk Han MD Abstract BACKGROUND. The purpose of the current study was to investigate the role of amifostine and epoetin-, in reducing severe toxicities during concurrent chemo-hyperfractionated radiotherapy (CCRT) for limited disease small cell lung cancer (LD-SCLC). METHODS. Seventy-six patients with LD-SCLC were enrolled. The treatment schedule was consisted of two 28-day cycles of cisplatin at a dose of 30 mg/m2 (Days 1 and 8) and irinotecan at a dose of 60 mg/m2 (Days 1, 8, and 15) followed by two 21-day cycles of cisplatin at a dose of 60 mg/m2 (Day 1) and etoposide at a dose of 100 mg/m2 (Days 1-3) with concurrent twice-daily thoracic radiotherapy for a total of 45 grays. Patients were randomly assigned at registration to either amifostine at a dose of 500 mg or epoetin-, at a dose of 10,000 IU subcutaneously 3 times weekly (n = 36 patients and 40 patients, respectively). Fifteen of 36 patients assigned to the amifostine arm did not receive amifostine because of a lack of supply. RESULTS. Amifostine treatment was associated with higher febrile neutropenia (P = .003) and grade 2 or 3 nausea (according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) (P = .03). It also demonstrated a trend toward higher grade 4 leukopenia (P = .05). Grade 3 esophagitis was reported in 30% of patients treated with amifostine and 9% of patients treated with epoetin-, (P = .059). Epoetin-, treatment was associated with less grade 2 or 3 anemia (P = .031) and lower decreases in hemoglobin level during CCRT (P = .016). The median survival times for both treatment arms were comparable (22.6 months in the amifostine arm vs 25.6 months in the epoetin-, arm; P = .447). CONCLUSIONS. Although amifostine administered 3 times weekly during CCRT did not significantly reduce severe toxicities, epoetin-, was effective in preventing severe anemia during CCRT in patients with LD-SCLC. Other radioprotective strategies to minimize severe toxicities should be investigated Cancer 2008. © 2008 American Cancer Society. [source] A multicenter, randomized, Phase II study of cisplatin, etoposide, and gemcitabine or cisplatin plus gemcitabine as first-line treatment in patients with poor-prognosis small cell lung carcinomaCANCER, Issue 4 2005Filippo De Marinis M.D. Abstract BACKGROUND The objective of this study was to evaluate the activity and toxicity of combined cisplatin, etoposide, and gemcitabine (PEG) and combined cisplatin plus gemcitabine (PG) in previously untreated patients with extensive-stage and poor-prognosis limited-stage small-cell lung carcinoma. METHODS One hundred forty patients (70 patients in two arms) were randomized to receive either cisplatin 70 mg/m2 on Day 1, etoposide 50 mg/m2 on Days 1,3, and gemcitabine 1000 mg/m2 on Days 1 and 8 or cisplatin 70 mg/m2 on Day 1 plus gemcitabine 1250 mg/m2 on Days 1 and 8. Both regimens were recycled every 21 days. RESULTS In total, 626 cycles were delivered (303 cycles of PEG and 323 cycles of PG), with a median of 4 cycles per patient in both arms. The objective response rate was 63% (95% confidence interval [95%CI], 49,71%) for PEG and 57% (95%CI, 43,67%) for PG, with the suggestion of a higher complete response rate in the PEG arm (18.6% and 4.3%, respectively). A similar time to disease progression (6 months in the PEG arm and 7 months in the PG arm) and a similar median survival (9.5 months in the PEG arm and 10 months in the PG arm) were observed in both arms. The PEG regimen was associated with more severe hematologic toxicity in terms of neutropenia, febrile neutropenia, and a higher rate of treatment delays and dose reductions, whereas nonhematologic toxicities did not differ between the two arms. CONCLUSIONS According to the results of this Phase II randomized trial, the PEG regimen produced a higher complete response rate but more toxicity compared with the PG regimen in patients with extensive-stage or poor-prognosis, limited-stage small cell lung carcinoma. Cancer 2005. © 2005 American Cancer Society. [source] CD4 lymphopenia as a risk factor for febrile neutropenia and early death after cytotoxic chemotherapy in adult patients with cancerCANCER, Issue 11 2004Christophe Borg M.D. Abstract BACKGROUND Lymphopenia is frequently observed in patients with cancer and correlates with the risk of febrile neutropenia and early death after chemotherapy. The phenotype of the depleted lymphocyte populations was investigated in the current study. METHODS Peripheral blood lymphocyte subsets (CD3, CD4, CD8, CD19, CD56) were quantified on Day 1 using fluorescence-activated cell sorting in a prospective study of 213 patients with cancer treated with chemotherapy in a single oncology ward during 12 months. Correlations between lymphocyte phenotype, clinical characteristics, and the risk of febrile neutropenia and early death within 31 days after chemotherapy were investigated in univariate and multivariate analyses. RESULTS Total lymphocyte count and CD3, CD4, and CD8 lymphocyte subsets were significantly lower in patients who experienced febrile neutropenia. Total lymphocyte count and CD3, CD4, CD8, CD19, and CD56 lymphocyte subsets were significantly lower in patients who died within 31 days after chemotherapy. Using logistic regression, CD4 lymphopenia (< 450/,L; odds ratio [OR] = 2.9, 95% confidence interval [CI] = 1.5,5.9) and the dose of chemotherapy (OR = 3,9, 95% CI = 2.0,7.8) were both identified as independent risk factors for febrile neutropenia. Fifty-four percent of patients with both risk factors experienced febrile neutropenia. CD4 lymphocyte count < 450/,L was also an independent risk factor for early death (OR = 7.7, 95% CI = 1.7,35). Thirteen percent of patients with a CD4 lymphocyte count , 450/,L died within 31 days after chemotherapy. Eighty-seven percent (14 of 16) of patients who died before Day 31 had a CD4 lymphocyte count < 450/,L. CONCLUSIONS A low CD4 count was an independent risk factor for febrile neutropenia and early death in patients receiving cytotoxic chemotherapy. Cancer 2004. © 2004 American Cancer Society. [source] Treatment of advanced colorectal carcinoma with oxaliplatin and capecitabineCANCER, Issue 3 2004A Phase II trial Abstract BACKGROUND The current study was designed to evaluate the antitumor activity and toxicity of capecitabine and oxaliplatin in previously untreated patients with advanced colorectal carcinoma. The primary endpoint of the study was to determine the objective response rate, and a secondary endpoint was to measure the time to disease progression. METHODS A 2-stage trial was planned with an accrual goal of 35 patients. The treatment included oxaliplatin given at a dose of 130 mg/m2 on Day 1 of each 3-week cycle. Initially, capecitabine at a dose of 2000 mg/m2/day in 2 divided doses was given on Days 1,14 of each cycle, but this was reduced to a dose of 1500 mg/m2/day because of toxicity. Patients were followed by computed tomography scans every two cycles to evaluate treatment response, and toxicity was monitored. RESULTS The first 13 patients on the trial received the higher dose of capecitabine. Although 5 responses (38.5%) were noted, 5 patients were hospitalized with diarrhea and dehydration. This toxicity led to a decrease in the dose of capecitabine to 1500 mg/m2/day and an additional 35 patients were treated. At the lower dose, the partial response rate was 37.1% (95% confidence interval [95% CI], 21.5,55.1%). The estimated median progression-free survival was 6.9 months (95% CI, 4.4,8.2 months). At the lower dose, four patients were hospitalized with diarrhea/dehydration (with one death reported), one with febrile neutropenia, and one with ventricular fibrillation. Overall, Grade (according to version 2.0 of the National Cancer Institute Common Toxicity Criteria) 3-4 diarrhea was reported to develop in 20% of those patients treated at the capecitabine dose of 1500 mg/m2/day compared with 62% of patients treated at the dose of 2000 mg/m2/day. CONCLUSIONS The combination of oxaliplatin and capecitabine is an active and convenient regimen for the treatment of patients with advanced colorectal carcinoma and should be compared with other front-line regimens as therapy for disease. Cancer 2004. © 2003 American Cancer Society. [source] | ||||||||||