Prolonged, alternating chemotherapy for extensive small cell lung cancer. A Southwest oncology Group study

Etoposide may be schedule dependent in small cell lung cancer (SCLC), and some data suggest a benefit for increased dose intensity in this disease. This study attempted to optimize dose intensity using an outpatient program that included prolonged, oral etoposide administration.

Cisplatin-etoposide (PE) and cyclophosphamide, doxorubicin, and vincristine (CAV) were alternated at monthly intervals in patients with extensive SCLC. PE was given as cisplatin 50 mg/m2 on days 1 and 8 intravenously (i.v.) and etoposide 50 mg/m2/day for 14 days by mouth. CAV was administered as cyclophosphamide 60 mg/m2/day for 21 days orally, doxorubicin 20 mg/m2/week for three doses, and vincristine 2 mg i.v. on day 1 only. At the end of 4 months, responding patients received an additional course of PE alternating with CAV, and whole-brain irradiation (3000 cGy in 15 fractions) was delivered to clinical complete responders (CR).

Among 61 eligible patients, 4 achieved CR, and 11 had a partial remission, by strict Southwest Oncology Group criteria. An additional 20 patients demonstrated greater than 50% tumor shrinkage on one disease assessment but did not have confirming measurements at all sites 4 weeks later. The overall response rate was 57%, including the latter group. The toxicity was primarily hematologic, with three treatment-related deaths from neutropenic infection (5%). Grade 4 neutropenia (< 500/microliters) occurred in nine patients (15%) and Grade 4 thrombocytopenia (< 25,000/microliters), in three (5%). Analysis of the delivered dose intensity (in milligrams per square meter per week) as a function of that which was planned revealed a mean of 93% for all courses.

Although substitution of prolonged oral etoposide in PE and oral cyclophosphamide in CAV proved to be feasible, these results suggest no advantage over those from other reported series using these alternating regimens in which the agents are pulsed. Experience with alternating PE-CAV for extensive SCLC is reviewed.