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Low-dose Cisplatin (low-dose + cisplatin)

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Medical Sciences	100%

Selected Abstracts

Low-dose metronomic chemotherapy with cisplatin: can it suppress angiogenesis in H22 hepatocarcinoma cells?

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 1 2010
Fang-Zhen Shen
Summary Low-dose chemotherapy drugs can suppress tumours by restraining tumour vessel growth and preventing the repair of damaged vascular endothelial cells. Cisplatin is a broad-spectrum, cell cycle-non-specific drug, but has serious side effects if used at high doses. There have been few reports on the anti-angiogenic effects of low-dose cisplatin and hence the effect of low-dose metronomic (LDM) chemotherapy on the proliferation and neovascularization of H22 hepatocarcinoma cells is discussed in this research. The influence of LDM chemotherapy with cisplatin on human umbilical vascular endothelial cells (HUVECs) and proliferation of the HepG2 human hepatocarcinoma cell line were measured using MTT assays. The LDM group was treated with cisplatin 0.6 mg/kg/day; the control group with saline 0.2 ml; the maximum tolerated dose (MTD) group with cisplatin 9 mg/kg/day. Vascular endothelial growth factor (VEGF) and matrix metallopeptidase 2 (MMP-2) were detected using immunohistochemical staining. A chicken chorio-allantoic membrane (CAM) model was used to check the inhibitory effect of LDM chemotherapy with cisplatin on neovascularization in vivo. Low-dose cisplatin inhibited HUVEC proliferation in a dose- and time-dependent manner, but was ineffective in inhibiting HepG2 cell proliferation. Tumour growth was delayed in mice receiving LDM cisplatin, without apparent body weight loss, compared with mice that received MTD cisplatin. Microvessel density and expression of VEGF and MMP-2 were much lower in mice receiving LDM cisplatin than in the control and MTD groups. Continuous low-dose cisplatin suppressed CAM angiogenesis in vivo. LDM chemotherapy with cisplatin can inhibit the growth of blood vessel endothelial cells in vitro and shows anti-angiogenic ability in vivo. [source]

Efficacy of chemoradiotherapy with low-dose cisplatin and continuous infusion of 5-fluorouracil for unresectable squamous cell carcinoma of the esophagus

DISEASES OF THE ESOPHAGUS, Issue 6 2009
Ryo Takagawa
SUMMARY We retrospectively investigated the efficacy of a chemoradiotherapy regimen using daily low-dose cisplatin and continuous 5-fluorouracil infusion in 71 registered patients with unresectable esophageal cancer. The overall response rate (complete response plus partial response) was 59%. The major toxicities observed were leukopenia and anorexia. The 1- and 3-year overall survival rates were 54.6% and 18.4%, respectively. A low preoperative C-reactive protein level was found to be associated with a good response. The pretreatment performance status and response results were both shown to be prognostic factors for overall survival. These findings confirmed that the chemoradiotherapy regimen had curative potential for unresectable esophageal cancer. [source]

Concomitant low-dose cisplatin and three-dimensional conformal radiotherapy for locally advanced squamous cell carcinoma of the head and neck: Analysis of survival and toxicity,

HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 3 2006
Harold Lau MD
Abstract Background. Our center sought to implement a simple chemoradiotherapy schedule for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) with minimal toxicity to achieve rates of overall survival comparable to other schedules. Methods. The chemoradiotherapy schedule consisted of daily radiation to 70 Gy over 7 weeks with concurrent cisplatin 20 mg/m2 during days 1 to 4 of weeks 1 and 5. Acute and late toxicities were recorded according to the Radiation Therapy Oncology Group (RTOG) and common toxicity criteria (CTC) grading. The overall, disease-specific, and locoregional recurrence,free survival were calculated using the STATA statistics package. Possible factors influencing these endpoints were analyzed. Results. Fifty-seven patients were treated, and 56 patients were evaluable for follow-up. Median follow-up of alive patients was 16.1 months. There was an 82% complete response rate to chemoradiotherapy. The 2-year Kaplan,Meier overall, disease-specific, and locoregional recurrence,free survival rates were 62%, 67%, and 63%. Acute grade 3 and 4 radiation toxicity was noted in 61% and 2%, respectively. Grade 3 or 4 hematologic toxicity was noted in 7% of patients. Factors influencing overall survival included: Karnofsky performance status, receiving more than 50% of planned chemotherapy, age, and initial hemoglobin level. Conclusion. This regimen is tolerable and achieves overall survival and locoregional control rates comparable to other chemoradiotherapy schedules. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source]

Combination of thalidomide and cisplatin in an head and neck squamous cell carcinomas model results in an enhanced antiangiogenic activity in vitro and in vivo

INTERNATIONAL JOURNAL OF CANCER, Issue 8 2007
Gergely P. Vasvari
Abstract Thalidomide is an immunomodulatory, antiangiogenic drug. Although there is evidence that it might be more effective in combination with chemotherapy the exact mechanism of action is unclear. Therefore, we investigated its effect in combination with metronomically applied cisplatin in a xenotransplant mouse model characteristic for advanced head and neck squamous cell carcinomas, its possible synergistic action in vitro, and which tumor-derived factors might be targeted by thalidomide. Although thalidomide alone was ineffective, a combined treatment with low-dose cisplatin inhibited significant tumor growth, proliferation and angiogenesis in vivo as well as migration and tube formation of endothelial cells in vitro. Noteworthy, the latter effect was enhanced after coapplication of cisplatin in nontoxic doses. An inhibitory effect on tumor cell migration was also observed suggesting a direct antitumor effect. Although thalidomide alone did not influence cell proliferation, it augmented antiproliferative response after cisplatin application emphasizing the idea of a potentiated effect when both drugs are combined. Furthermore, we could show that antiangiogenic effects of thalidomide are related to tumor-cell derived factors including vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor and Il-8 some known and with, granulocyte colony stimulating growth factor and granulocyte macrophage colony stimulating growth factor, some new target molecules of thalidomide. Altogether, our findings reveal new insights into thalidomide-mediated antitumor and antiangiogenic effects and its interaction with cytostatic drugs. © 2007 Wiley-Liss, Inc. [source]

Low-dose metronomic chemotherapy with cisplatin: can it suppress angiogenesis in H22 hepatocarcinoma cells?

Metastatic urothelial cancer showing an efficacy by low-dose cisplatin

INTERNATIONAL JOURNAL OF UROLOGY, Issue 5 2002
Hideyasu Matsuyama
Abstract A 69-year-old man who had developed multiple distant metastases on retrocaval lymph nodes after four courses of Methotraxate, Vinblastine, Adriamycin, Cisplatin (MVAC) chemotherapy was successfully treated by intravenous infusion of low-dose cisplatin (CDDP) (10 mg/time, once per week) and oral administration of 600 mg/day 5,-deoxy-5-fluorouridine (5,-DFUR), a pro-drug of 5-FU, in an outpatient setting. A partial response (62% reduction rate) was confirmed by abdominal computed tomography (CT) scan after 7 months. Although the CDDP dosage had been reduced to 5 mg/week 1 year previously, the tumor was still reducing in size in November 2000. Combination therapy of 5,-DFUR with low-dose CDDP could become an option for advanced bladder cancer that compromises the patient's quality of life, especially when used in an outpatient setting. [source]

Postoperative reduced dose of cisplatin concomitant with radiation therapy in high- risk head and neck squamous cell carcinoma,

CANCER, Issue 11 2009
Giovanni Franchin MD
Abstract BACKGROUND: The role of low doses of cisplatin and concomitant postoperative radiotherapy in high risk head and neck squamous cell carcinoma has not yet been defined. METHODS: Patients treated with definitive surgery, who had histological evidence of involvement of more than 2 lymph nodes, extracapsular extension of disease, perineural and/or intravascular invasion, involved or close surgical margins, received postoperative radiotherapy plus 75 mg/m2 of cisplatin every 3 weeks during the radiotherapy cycle. The primary endpoints were to evaluate treatment compliance and overall, cause-specific, and disease-free survival. RESULTS: A total of 142 patients were enrolled. With a median follow-up of 40 months, 5-year overall survival was 68%, cause-specific survival 78% and disease-free survival 82%. At multivariate analysis surgical margins status and extracapsular lymph node invasion were the only statistically significant prognostic factors. Fifty-three percent of the patients developed severe mucositis and 14% hematologic toxicity of grade 3. The 3 planned concomitant chemotherapy cycles were delivered to 48% of the patients. CONCLUSIONS: Postoperative radiotherapy and concomitant low-dose cisplatin was an effective treatment in high risk head and neck patients. The total toxicity observed was lower compared with that reported with higher doses of cisplatin, although the delivery of all the 3 planned chemotherapy cycles was challenging. The distant failure rate was high, which was an unsatisfactory result. Cancer 2009. © 2009 American Cancer Society. [source]

Adenocarcinoma arising from a mature cystic teratoma of the testis

INTERNATIONAL JOURNAL OF UROLOGY, Issue 9 2003
TOSHINORI KASAI
Abstract A 52-year-old male diagnosed pathologically with metastatic adenocarcinoma of the skin was referred to our department. Physical examination revealed a right scrotal mass the size of child's head and several skin tumors. Right high orchiectomy and resection of skin tumors were performed. Histopathological examination revealed a well-differentiated, mucinous adenocarcinoma originating from the gastrointestinal epithelium in a mature cystic teratoma (dermoid cyst) of the testis and metastatic mucinous adenocarcinoma of the skin. We made a diagnosis of teratoma with malignant transformation (TMT) of the testis. Combination chemotherapy with low-dose cisplatin/5,-deoxy-5-fluorouridine (CDDP/5,-DFUR) was initiated, but the patient died 8 months after orchiectomy. At autopsy, similar mucinous adenocarcinoma of the testis and the skin were observed at the metastatic sites. [source]