Takamune Sugiura

Randomised phase III trial of irinotecan combined with cisplatin for advanced non-small-cell lung cancer

To determine a standard combination chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC), we conducted a phase III trial of irinotecan (CPT-11) to test the hypotheses that CPT-11+cisplatin is superior to cisplatin+vindesine and that CPT-11 monotherapy is not inferior to cisplatin+vindesine. A total of 398 patients with previously untreated NSCLC were randomised to receive cisplatin+CPT-11 (CPT-P), cisplatin+vindesine (VDS-P) or CPT-11 alone (CPT). In the CPT-P arm, CPT-11 60 mg m−2 was administered on days 1, 8 and 15, and cisplatin 80 mg m−2 was administered on day 1. In the VDS-P arm, cisplatin 80 mg m−2 was administered on day 1, and vindesine 3 mg m−2 was administered on days 1, 8 and 15. In the CPT arm, CPT-11 100 mg m−2 was administered on days 1, 8 and 15. The median survival time was 50.0 weeks for patients on CPT-P, 45.6 weeks for those on VDS-P and 46.0 weeks for those on CPT (P=0.115, CPT-P vs VDS-P; P=0.089, CPT vs VDS-P), and the hazard ratio was 0.85 (95% confidence interval (CI): 0.65–1.11) for CPT-P vs VDS-P and 0.83 (0.64–1.09) for CPT vs VDS-P. The response rate was 43.7% for patients on CPT-P, 31.7% for those on VDS-P and 20.5% for those on CPT. Major adverse reactions were grade 4 neutropenia observed in 37, 54 and 8% of the patients on CPT-P, VDS-P and CPT, respectively; and grades 3 and 4 diarrhoea observed in 12, 3 and 15% of the patients, respectively. CPT-P therapy produces comparable survival to VDS-P in patients with advanced NSCLC. CPT-11 monotherapy is not inferior to VDS-P in terms of survival. The CPT-11-containing regimen is one of the most efficacious and well tolerated in the treatment of advanced NSCLC.

Randomised phase II study of docetaxel/cisplatin vs docetaxel/irinotecan in advanced non-small-cell lung cancer: a West Japan Thoracic Oncology Group Study (WJTOG9803)

Docetaxel plus cisplatin and docetaxel plus irinotecan are active and well-tolerated chemotherapy regimens for advanced non-small-cell lung cancer (NSCLC). A randomised phase II study compared their efficacy and toxicity in 108 patients with stage IIIb/IV NSCLC, who were randomised to receive docetaxel 60 mg m−2 and cisplatin 80 mg m−2 on day 1 (DC; n=51), or docetaxel 60 mg m−2 on day 8 and irinotecan 60 mg m−2 on day 1 and 8 (DI; n=57) every 3 weeks. Response rates were 37% for DC and 32% for DI patients. Median survival times and 1- and 2-year survival rates were 50 weeks (95% confidence interval: 34–78 weeks), 47 and 25% for DC, and 46 weeks (95% confidence interval: 37–54 weeks), 40 and 18% for DI, respectively. The progression-free survival time was 20 weeks (95% confidence interval: 14–25 weeks) with DC and 18 (95% confidence interval: 12–22 weeks) with DI. Significantly more DI than DC patients had grade 4 leucopenia and neutropenia (P<0.01); more DC patients had grade ⩾2 thrombocytopenia (P<0.01). Nausea and vomiting was more pronounced with DC (P<0.01); diarrhoea was more common with DI (P=0.01). Three treatment-related deaths occurred in DC patients. In conclusion, although the DI and DC regimens had different toxicity profiles, there was no significant difference in survival.

Phase II Trial of Amrubicin for Second-Line Treatment of Advanced Non-small Cell Lung Cancer Results of the West Japan Thoracic Oncology Group Trial (WJTOG0401)

Background: Amrubicin is a synthetic anthracycline drug that is a potent inhibitor of topoisomerase II. We have performed a multicenter phase II trial to evaluate the efficacy and safety of amrubicin for patients with previously treated non-small cell lung cancer (NSCLC). Methods: Patients with advanced NSCLC who experienced disease recurrence after one platinum-based chemotherapy regimen were eligible for enrollment in the study. Amrubicin was administered by intravenous injection at a dose of 40 mg/m2 on 3 consecutive days every 3 weeks. Results: Sixty-one enrolled patients received a total of 192 treatment cycles (median, 2; range, 1–15). Response was as follows: complete response, 0; partial response, seven (11.5%); stable disease, 20 (32.8%); and progressive disease, 34 (55.7%). Median progression-free survival was 1.8 months, whereas median overall survival was 8.5 months, and the 1-year survival rate was 32%. Hematologic toxicities of grade 3 or 4 included neutropenia (82.0%), leukopenia (73.8%), thrombocytopenia (24.6%), and anemia (27.9%). Febrile neutropenia occurred in 18 patients (29.5%). One treatment-related death due to infection was observed. Nonhematologic toxicities were mild. Conclusions: Amrubicin is a possible alternative for second-line treatment of advanced NSCLC, although a relevant hematological toxicity is significant, especially with a febrile neutropenia.

Spontaneous pneumothorax due to bronchopleural fistula following reirradiation for locoregionally recurrent squamous cell lung cancer

Spontaneous pneumothorax following radiotherapy for pulmonary malignancy is an unusual clinical condition. Here, we report a case of a 78‐year‐old male suffering from dyspnea during radiotherapy for squamous cell lung cancer of the right main bronchus. Imaging studies and fiberoptic bronchoscopy revealed that pneumothorax was due to a bronchopleural fistula.