Phase I study of the combination of nedaplatin and weekly paclitaxel in patients with advanced non-small cell lung cancer.

PURPOSE: This trial was conducted to determine the maximum tolerated dose (MTD), principal toxicity, and recommended dose for phase II study of the combination of nedaplatin and weekly paclitaxel in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Patients with previously untreated NSCLC, either stage IIIB with pleural effusion or stage IV, were eligible if they had a performance status of 0-2, were 75 years or younger, and had adequate organ function. The respective doses of nedaplatin (day 1) and weekly paclitaxel (days 1, 8, and 15) studied were 80/60, 80/70, 80/80, 80/90, and 100/90 (mg m(-2)), repeated every 4 weeks. RESULTS: From May 2004 through June 2005, 21 patients (18 men and 3 women; median age, 63 years; age range, 53-75 years) were enrolled. The MTD was determined to be 100 mg m(-2) of nedaplatin and 90 mg m(-2) of weekly paclitaxel. Dose-limiting toxicities at the MTD were neutropenic fever and hepatic dysfunction. We recommend doses of 80 mg m(-2) of nedaplatin and 90 mg m(-2) of weekly paclitaxel for phase II study. Grade 3-4 hematologic toxicities included neutropenia in 29% of patients, thrombocytopenia in 0%, and anemia in 5%. Although the most frequent non-hematologic toxicity was hepatic dysfunction, all cases were only mildly to moderately severe. Although two patients had grade 3 or 4 pulmonary toxicity due to Pneumocystis carinii pneumonia, these patients recovered after receiving trimetoprim-sulfamethoxazole, steroid therapy, and supplemental oxygen. There were no treatment-related deaths. The overall response rate was 19.0% (95% confidence interval, 5.4-41.9%), and all responses were in patients receiving the recommended doses. The median dose-intensities for nedaplatin and paclitaxel were 91.6 and 87.1%, respectively, of the planned doses. CONCLUSION: This combination chemotherapy is active and well tolerated and warrants phase II study.

Phase II study of biweekly administration of docetaxel and irinotecan in patients with refractory or relapsed advanced non-small cell lung cancer.

We examined the safety and efficacy of the combination of docetaxel and irinotecan administered biweekly in patients with refractory or relapsed advanced non-small cell lung cancer (NSCLC). Patients with previously treated NSCLC of stage III or IV were eligible if they had a performance status of 2 or less, were 75 years or younger, and had adequate organ function. From May 2003 through February 2006, 35 patients (27 men and 8 women; median age 64 years; age range 41-75 years) were enrolled. Patients were treated every 4 weeks with docetaxel (33 mg/m(2) on days 2 and 16) plus irinotecan (50 mg/m(2) on days 1 and 15). None of the 35 patients achieved a complete response, but five achieved a partial response, for an overall response rate of 14.3% (95% confidence interval, 4.8-30.3%). The median survival time was 8 months (range 2-29 months). The median time to progression was 3 months (range 1-12 months). Grade 3 to 4 hematologic toxicities included leukopenia in 48.6% of patients, neutropenia in 54.3%, and anemia in 25.7%. No patients had grade 3 to 4 diarrhea or nausea and vomiting. Although one patient had grade 3 drug-induced interstitial pneumonia, all side effects were manageable, and there were no treatment-related deaths. In conclusion, the combination of docetaxel and irinotecan administered biweekly is a safe and effective treatment for refractory or relapsed NSCLC. However, the search for even more active regimens should be continued.

The combination of cisplatin and vinorelbine with concurrent thoracic radiation therapy for locally advanced stage IIIA or IIIB non-small-cell lung cancer.

AIMS: The aims of this study were to assess the efficacy and toxicity of concurrent chemoradiotherapy with divided schedule of cisplatin and vinorelbine in patients with locally advanced non-small-cell lung cancer (NSCLC). METHODS: Patients with previously untreated, unresectable, and stage IIIA or IIIB NSCLC were eligible if they had a performance status of 0 or 1, were 75 years or younger, and had adequate organ function. Twenty-six patients (24 men and 2 women; median age, 66 years; age range, 42-75 years) were enrolled. Both cisplatin (40 mg/m(2)) and vinorelbine (20 mg/m(2)) were given on days 1 and 8 every 3 weeks. Beginning on day 2 of chemotherapy, thoracic radiotherapy was given for approximately 6 weeks (2 Gy per fraction; total dose, 60 Gy). RESULTS: Five of the 26 patients achieved a complete response, and 16 achieved a partial response for an overall response rate of 80.8% (95% confidence interval, 60.6-93.4%). The median survival time was 23 months (range, 4-43 months). Overall survival rates at 1 and 2 years were 80 and 56%, respectively. Hematologic toxicities included grade 3-4 neutropenia in 84.6% of patients, grade 3-4 thrombocytopenia in 3.8%, and grade 3-4 anemia in 61.5%. Two patients (7.7%) had grade 3 radiation esophagitis that resolved completely without dilation. Grade 3-4 radiation pneumonitis occurred in two patients (7.7%) and was treated with corticosteroids. Both patients had a good partial resolution of symptoms and radiographic abnormalities. There were no treatment-related deaths. The actual delivered dose intensities for both cisplatin and vinorelbine were 79.5%. Radiotherapy was completed in 96% of patients. CONCLUSION: Concurrent chemoradiotherapy with cisplatin and vinorelbine administered on a divided schedule is effective and well tolerated in patients with locally advanced NSCLC.

Phase II study of irinotecan and carboplatin in patients with the refractory or relapsed small cell lung cancer.

We examined the safety and efficacy of the combination of irinotecan plus carboplatin in patients with refractory or relapsed small cell lung cancer (SCLC). Patients with previously treated SCLC were eligible. Patients were treated every 3 weeks with carboplatin (with a target area under the concentration versus time curve of 5 mg min/ml using the Calvert formula on day 1) plus irinotecan (50 mg/m(2) on days 1 and 8). From May 2000 to January 2002, 24 patients were eligible. None of the 22 patients achieved a complete response, but 15 achieved a partial response with an overall response rate of 68.2% (95% confidence interval, 45.1-86.1%). In 13 patients with sensitive disease, the response rate was 92.3% (95% confidence interval, 64.0-99.8%). The median survival time (MST) was 194 days (range 27-605 days). The MST did not differ significantly between patients with sensitive disease (245 days) and those with refractory disease (194 days, P=0.88). One patient died of treatment-related sepsis. Grade 3-4 hematologic toxicities included leukopenia in 58% of patients, neutropenia in 63%, thrombocytopenia in 58%, and anemia in 67%. Grade 3 diarrhea developed in 21% of patients and grade 3-4 infection in 13%. No patients had grade 4 diarrhea or grade 3-4 nausea and vomiting. This regimen is effective and well tolerated in patients with relapsed or refractory SCLC. However, the search for even more active regimens should be continued.