3

In a Japanese study 5 that included only patients with extensive disease, survival rates with a combination of irinotecan plus cisplatin were superior to those with etoposide and cisplatin, with one-year survival being 58.4% versus 37.9%, and median survival 12.8 months versus 9.4 months; also response rates of 84% versus 68% were in favor of irinotecan and cisplatin. Grade 3 and 4 diarrhea occurred in 16% in the irinotecan combination compared with none in the etoposide arm. The study was prematurely stopped after the enrollment of 152 patients out of the planned 230 patients, as recommended by a preplanned interim analysis. A confirmatory randomized study was initiated in the US by Hanna et al, 6 with randomization of 331 patients to either irinotecan or etoposide, both in combination with cisplatin. An unequally balanced randomization was performed, allocating one-third of patients to etoposide and two-thirds to the irinotecan arm. In both arms, four cycles were delivered every three weeks. After the enrollment of 30 patients, inclusion was restricted to patients in performance status 0 and 1 due to an excessive toxic death rate among patients with performance status 2. As in the Japanese study, myelotoxicity and febrile neutropenia were more frequent in the etoposide arm, whereas gastrointestinal toxicity was more common in the irinotecan arm, including 21% of patients suffering from grade 3-4 diarrhea. Unfortunately, this study could not confirm the encouraging

Table 11.3.1 Agents used in SCLC: most frequently chosen

agents for inclusion in combination regimens

Alkylating agents Cisplatin Carboplatin Ifosfamide Cyclophosphamide

Antimitotic agents Vincristine Paclitaxel

Topoisomerase inhibitors Etoposide Irinotecan Topotecan Doxorubicin

Table 11.3.2 Commonly used regimens in SCLC

Regimen Dosage and schedule

PE Cisplatin 25 mg/m 2 iv on days 1-3 or 60-80 Etoposide 100 mg/m 2 iv on days 1-3 or 115 mg/m 2 iv days 3-5 q 3 wks CE Carboplatin AUC 6 day 1 iv Etoposide 100-120 mg/m 2 iv days 1-3 q 3 wks ICE Ifosfamide 5000 mg/m 2 iv day 1 + Carboplatin 300-400 mg/m 2 iv day 1 Etoposide 100-200 mg/m 2 iv days 1-3 + mesna 500 mg/m 2 day 1 and 3000 mg day 2 – with or 1.0 mg/m 2 day 14

without midcycle vincristine

Japanese data and no significant differences were seen in the overall survival, time to progression, or response rate. Median survival times were 9.3 versus 10.2 months in the irinotecan/cisplatin and etoposide/cisplatin arms, respectively.