Vinorelbine and Cisplatin Injection: Interaction Details

a) Concomitant administration of CISplatin and vinorelbine is efficacious, safe and well tolerated in patients with metastatic breast cancer previously treated with anthracyclines. Fifty-three patients with assessable metastatic breast cancer with previous exposure to anthracyclines were classified into one of three categories anthracycline refractory patients, anthracycline resistance patients, previously treated with anthracyclines or relapsed patients. Treatment consisted of CISplatin administered intravenously over one hour at the dose of 75 mg/ m2 on day 1 of the cycle. Vinorelbine was administered at the dose of 25 mg/m2 on days 1 and 8. The regimen was repeated every three weeks until evidence of disease progression and for a maximum of six courses. Four patients achieved a complete response and twenty-two patients achieved a partial response with an overall response rate of 49%. Twenty-two patients had progressive disease, whereas, stable disease was observed in five patients. Grade 3 and 4 neutropenia was the main toxicity. The results of this study indicate that CISplatin-vinorelbine may have a place as second-line treatment alternative to taxanes or other less active regimens, although further studies are necessary for comparison of the activity of this regimen with taxane regimens ¹..

b) A study demonstrated that the combination CISplatin, vinorelbine, and ifosfamide had a high response rate and a slight increase in survival time for patients with inoperable stage III or IV non-small-cell lung cancer (NSCLC). A constant dose of CISplatin was administered on day 5 to all patients. Arm A consisted of 20 patients who were administered vinorelbine 25 mg/m2 on days 1 and 5 and ifosfamide 3 g/m2 on day 5. In arm B, 35 patients received vinorelbine 20 mg/m2 on day 5. The response rate was 50% in arm A and 30% in arm B. The median survival times for arm A was 40 weeks and for arm B 42 weeks, whereas the summation dose intensity (SDI) was 1.94 and 1.7, respectively. In arm A more than 28.9% of the patients had higher than grade III leukopenia versus only 17.2% in arm B. The survival time was similar in both arms. A high response rate may not be directly related to a high survival rate. Further studies are needed to determine proper dosage of chemotherapeutic agents with respect to response rate and the relationship with survival rate that is needed ².

c) Increasing the dose intensity of vinorelbine plus cisplatin given daily for four consecutive days every three weeks has a comparable therapeutic activity in patients with advanced lung cancers. Thirty-one patients with previously untreated advanced non-small cell lung cancer were administered vinorelbine 15 mg/m2 and CISplatin 20 mg/m2 intravenously daily for 4 days and repeated every 21 days. A total of 96 cycles were administered (median 3, range 1-6); 42% of vinorelbine and 39% of CISplatin injections were delayed or dose-reduced due to toxicity. The dose intensity of vinorelbine and cisplatin were 17.7 mg/m2/week and 24 mg/m2/week, respectively. Overall, response rate was 40% (12/30, one CR). Granulocytopenia occurred in 77% of patients and thrombocytopenia in 6%. The median progression-free survival and overall survival time after a median follow-up of 7.5 months were 5 months (95% CI, 3.8-6.2) and 8 months (95% CI, 4.5-11.5), respectively. Despite supportive care this 4-day schedule of vinorelbine and cisplatin is not indicated outside a clinical trial due to increased hematological toxicities and similar efficacy ³.