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Background: To test the clinical activity and toxicity profile of the combination regimen of vinorelbine and cisplatin in a series of patients with carcinoma of the cervix uteri with de novo metastatic disease or recurrent disease after previous therapy. The main aims of the study included analysis of objective response rates, toxicity, and time to progression. Patients and Methods: Forty-two eligible patients were enrolled into the trial and treated with cisplatin 80 mg/m[sup 2] on day 1 and vinorelbine 25 mg/m[sup 2] on day 1 and 8. This regimen was repeated every 21 days upon resolution of toxicity for 3 cycles before response assessment. Enrolled patients had a median age of 53 years, a median ECOG performance status of 1, and mostly a squamous cell histology (86%). Sixteen patients (38%) were treatment-naive since first diagnosed with widespread metastatic disease, 7% had only previous surgery, 31% radiotherapy, and 24% both radiation and surgical therapy. In previously radiated patients, 21% of patients had disease only within the radiation fields, 21% only outside the radiation fields, and 12% both inside and outside the radiotherapy portals. Results: All patients were evaluable for response analysis. A complete response was achieved in 5 patients (12%), and a partial response in 15 cases (36%) for an overall response rate of 48% (95% CL 22–52%). Patients with recurrent disease within the previous radiation field (including those also with disease outside the radiation fields) showed a 28% overall response rate with no complete response, while patients with disease previously untreated with radiotherapy or with tumour deposits only outside of ratiation portals yielded a 57% overall response rate with a 18% complete response rate. Only 1 out of 8 patients with performance status 2 showed a major response (12%). Median time to progression was 5.6 months (range 2.0–14 months). The median overall survival of the whole series was 9.1 months. Hematological toxicity was the most frequent side-effect. Grade 3 vomiting was recorded in 9 patients (21%), and mild mucositis in 14% of patients. Grade 3 neutropenia was observed in 21% of patients, while grade 4 in 12% of cases with neutropenic fever was seen in 4 cases. Sixteen patients (38%) complained of grade 1–2 constipation, while grade 1–2 peripheral neuropathy was seen in 8 patients (19%). Conclusions: The results achieved in this trial suggest that the combination regimen of vinorelbine and cisplatin may be safely given to patients with metastatic and/or recurrent carcinoma of the uterine cervix. This regimen is active at least in terms of objective response rates. Although satisfactory results are still lacking, these results suggest that the vinorelbine-cisplatin regimen is worthy of further studies and may represent the basis for the development of new active regimens.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Colon cancer is the second leading cause of cancer death worldwide. Approximately three quarters of patients are diagnosed with disease limited to the bowel wall or surrounding lymph nodes. Over the past decade, significant progress has been made in the treatment of localized colon cancer. The use of adjuvant chemotherapy has improved prognosis in stage III disease, but much work remains to be done in optimizing adjuvant treatment. The FOLFOX4 regimen is now considered standard treatment for stage III disease. Combinations of irinotecan and 5-fluorouracil (5-FU) have not proven to be more effective than 5-FU/folinic acid. In stage II, the value of post-operative treatment remains controversial, but the identification of histopathological and molecular prognostic factors would allow selection of patients who can benefit from adjuvanttreatment. The inclusion of molecular targeted agents in combination regimens with cytotoxins, which have already proven effective in advanced disease, is the main field of development in the most recent protocols of adjuvant therapy. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A multicenter phase I-II trial was carried out with the aim of identifying the dose-limiting toxicity and the maximum tolerated dose of vinorelbine (VNR) in combination with pegylated liposomal doxorubicin at a dose of 20 mg/m[sup 2] every 15 days in patients with metastatic breast carcinoma. In the phase I part of the trial, VNR was given at a dose of 20 mg/m[sup 2] every 15 days to a group of 3 patients. In absence of unacceptable toxicity, VNR was escalated to 25, 30, and 35 mg/m[sup 2] for subsequent groups of 3 patients, until the dose-limiting toxicity was reached. No case of palmar-plantar erythrodysesthesia was recorded in these patients. Grade 4 neutropenia, grade 3 thrombocytopenia, and grade 3 mucositis were the dose-limiting toxicities recorded in patients treated with VNR 35 mg/m[sup 2] . These side effects caused a substantial decrease in programmed dose intensity. Therefore 30 mg/m[sup 2] was considered the maximum tolerated dose of VNR in combination with pegylated liposomal doxorubicin 20 mg/m[sup 2] , both given every 15 days. These dosages were employed for the treatment of further 18 patients included in phase II of the study. The overall response rate, calculated according to an intention to treat analysis, was 63% (95% CI: 44–80%), with 2 patients achieving a complete response. The median time to progression was 7.0 months or more (range 2–14 months). Median duration of objective responses was 8.4 months or more. The duration of the 2 complete responses was 9 and 14 months, respectively. Median duration of survival was 16.0 months or more (range from 4.0 to ≥24.0). Toxicity was generally mild and easily manageable. Neutropenia and mucositis were the most frequently recorded side effects. A case of palmar-plantar erythrodysesthesia was recorded in phase II of the study. In conclusion, the maximum tolerated dose of VNR in association with pegylated liposomal doxorubicin is 30 mg/m[sup 2] on a bimonthly schedule. Moreover, the combination of VNR and pegylated liposomal doxorubicin is active against metastatic breast carcinoma and is associated with a good toxicity profile. Further studies with this combination regimen are warranted.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]