A Phase 2 Study of VP-16 Ifosfamide and Cisplatin ( VIP ) Combination Chemotherapy Plus Early Concurrent Thoracic Irradiation ( TI ) for Limited Small Cell Lung Cancer
The emergence of combination chemotherapy and thoracic irradiation has improved both quality of life and survival in patients with small cell lung cancer. Most patients respond to initial treatment but unfortunately most also subsequqntly relapse and cure for most patients with small cell lung cancer remains elusive because of the develpment of drug resistant SCLC and metastasis to distant organs. The probability that thoracic irradiation would eliminate chemoresistant tumor should be inversely proportional to elapsed time. So early thoracic irradiation is recommended. Ifosfamide, an analogue of cyclophosphamide, is relatively nonmyelosuppressive drug. According to the recent report to evaluate the effect of ifosfamide, VIP(VP-16, ifosfamide, cisplatin)combination chemotherapy is assocated with an improved time to progression and overall survival over VP(VP-16, cisplatin)therapy in patients with extensive SCLC. We studied a phase II trial of VIP combination chemotherapy with early concurrent thoracic irradiation in previously untreated patients with small cell lung cancer. Treatment consisted of VP-l6 100mg/§³ i.v. days 1~3, Ifosfamide 1,000mg/§³ i.v. days 1~2 with mesna and cisplatin 100 mg/§³ i.v, day 1, cycles were repeated every 21 days. Concurrent thoracic irradiation was given as total 40Gy for 4 weeks beginning within 24 hours of cycle l, day l. Eligibility requirements included a histoioaically proven small cell lung cancer with limited stage, measurable disease, adequate renal function, bone marrow reserve. Patient characteristics(N=20) were male 17 patients, female 3 patients, median age 60 years(40~76 years). Responses were seen in all 20 patients including 8 CR's with a median follow up of 8.4 months. Hematologic side effects(WHO Gr¡A3) of evaluable 89 cycles of chemotherapy were anemia in 17 occaisions(19%), leukopenia in 10 occasions(11%). On adverse effects associated with radiation therapy 15 of all patients showed esophagitis but the severity was mild. Radiation pneumonitis was 5 patients(25%). Side effects of the treatment were tolerable and there was no treatment related mortality. In conclusion VIP combination chemotherapy with early concurrent thoracic irradiation in limited SCLC is considered to be an active regimen with acceptable toxicity but it is too early to comment on survival and effects of treatment.
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