Cancer Research and Treatment

Original Articles

A Phase 2 Study of VP-16 , Ifosfamide , and Cisplatin ( VIP ) Combination Chemotherapy Plus Concurrent Thoracic Irradiation for Limited Small Cell Lung Cancer: Seok Ah Im, Moon Hee Lee, Chul Won Jung, Dae Seog Heo, Yung Jue Bang, Young Soo Shim, Chan Il Park, Noe Kyeong Kim; J Korean Cancer Assoc. 1999;31(2):306-312.

Abstract PDF: PURPOSE
A phase II study of etoposide, ifosfamide, cisplatin combination chemotherapy and concurrent thoracic irradiation in patients with untreated limited small cell lung cancer (SCLC) was conducted to assess toxicities, response rate, response duration, and median survival.
MATERIALS AND METHODS
Patients with histologically confirmed SCLC with a ECOG criteria 2 and adequate renal function and bone marrow reserve were eligible. Each cycle consisted of VP-16 100 mg/m i.v, days 1-3, ifosfamide 1,200 mg/m i.v. days 1-3 with Mesna, and cisplatin 30 mg/m i.v. days 1-3. Cycles were repeated every 21 days. Concutrent thoracic itradiation was given as total 40-45 Gy for 4-5 weeks beginning within 24 hours of the third cycle. Patients with complete remission received prophylactic cranial irradiation after the 6th cycle.
RESULT
Forty two patients with limited SCLC were treated at Seoul National University Hospital between December 1993 and August 1996. Three patients were not evaluable because of lost to follow up (2 patients) and one treatment-related early death. Of 39 evaluable patients, responses were seen in 38 (97%) patients including 22 (56%) complete responses and 16 (41%) partial responses. The median remission duration was 65 wks. The median disease free survival was 60 wks. The median overall survival was not reached and 2-year survival was 69% with median duration of follow up of 63.5 wks. Hematologic side effects (WHO Gr>III/IV) of evaluable 228 cycles of chemotherapy were leukopenia in 34%, thrombocytopenia in 16%. One patient expired after prolonged leukopenia and sepsis. Nonhematologic side effects (WHO Gr>II) included nausea and vomiting (17%) and peripheral neuropathy (2%).
CONCLUSION
VIP combination chemotherapy with concurrent thoracic irradiation is effective and tolerable in limited SCLC.

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The Timing of Thoracic Radiotherapy for Limited Stage Small Cell Lung Cancer: Charn Il Park, Young Ho Kim, Yung Jue Bang, Dae Seog Heo, Noe Kyeong Kim; J Korean Cancer Assoc. 1995;27(3):442-451.

Abstract PDF: The purpose of this study was to evaluate the effect of the timing of thoracic radiotherapy in the combined modality therapy of limited stage small cell lung cancer with respect to local control and survivaL Two hundred and one patients with limited stage small cell lung cancer were treated at Seoul National University Hospital between April 1979 and February 1991. Of these, l12 patients received thoracic radiotherapy following 2 cycles of cyclophosphamide, adriamycin and vincristine( CAV) or VP-16, ifosphamide and cisplatin(VIP) alternating CAV schedule(sequential CT/RT) and 89 patients received thoracic radiotherapy concurrently with the 3rd cycle of etoposide and cisplatin(EP) or alternating EP/CAV schedule(concurrent CT/RT). Thoracic radiotherapy consisted of 40-45 Gy in 4-5 weeks. All patients received prophylactic cranial ir- radiation with 25 Gy in 10 fractions over 2 weeks. The over survival at 2 years for all 201 patients was 29.2%, with a median survival of 17 months. The median survival was 16 months for the sequential CT/RT and 18 months for the concurrent CT/RT. The survival rate in the sequential CT/RT schedule was 26.1% at 2 years, and 16.2% at 5 years, as compared with 32.5%, and 22.8% at 2 years and 5 years, respectively, in the concurrent CT/RT schedule. However, there was no significant difference between the two schedules(p=0.11). The local control rates for alternating EP/CAV regimens with concur- rent thoracic radiotherapy was significantly higher than that for other regimens(p=0.003). Seventy-two(48%) patients had local failure as the first site of failure, whereas 39(26%) patients had distant failure without local failures. Thirty-eight(26%) patients had local and distant failure. These results indicate that early, concurrent thoracic radiotherapy with alternating EP/ CAV regimens have the improved local control rates and a trend of the better survival in the combined modality treatment of limited stage small cell lung cancer.

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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: In Sook Woo, Young Suk Park, Young Lee Park, Jung Ae Lee, Myung Jae Park, Ki Suk Jung, In Gyn Hyun, Do Hoon Oh, Hoonsik Bae, Won Suk Kim, Keunchil Park, Hojoong Kim; J Korean Cancer Assoc. 1996;28(6):973-981.

Abstract PDF: 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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