Phase III trial of thoracic irradiation with or without cisplatin for locally advanced unresectable non-small-cell lung cancer: a Hoosier Oncology Group protocol.

PURPOSE: Here we report the results of a phase III study, to evaluate whether the addition of cisplatin to radiation therapy (XRT) would improve progression-free survival or overall survival for patients with locally advanced unresectable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Two hundred forty patients with biopsy-proven unresectable NSCLC without distant metastases or lower-stage medically inoperable patients were randomized to one of two treatment arms. Arm A consisted of thoracic XRT alone, 60 to 65 Gy total tumor dose in daily fractions of 1.80 to 2.00 Gy; and arm B consisted of identical XRT with the addition of cisplatin 70 mg/m2 every 3 weeks for three cycles beginning on the first day of irradiation. RESULTS: Two hundred fifteen patients were eligible and assessable. The overall response rate was 50% on the combination arm versus 38% on the XRT-alone arm (P = .076). The median progression-free survival time was 23 versus 22 weeks, respectively (P = .0537). The median survival time was 43 weeks on the combination arm versus 46 weeks on the XRT arm (Poverall = .3469). The 1-, 2-, and 5-year survival rates were 43%, 18%, and 5% on the combination arm versus 45% 13%, and 2% on the XRT arm, respectively. CONCLUSION: Cisplatin, administered every 3 weeks, does not significantly improve response rate, progression-free survival, or overall survival when added to thoracic XRT for locally advanced unresectable NSCLC.

A phase II trial of vinblastine plus dipyridamole in advanced renal cell carcinoma. A Hoosier Oncology Group Study.

One potential explanation for why renal cell carcinoma is usually poorly responsive to chemotherapy is intrinsic multidrug resistance. Dipyridamole (DP) is one of several agents known to bind to P-glycoprotein and potentially reverse multidrug resistance in vitro, and dosages needed to obtain appropriate levels in vivo appear to be well tolerated. The current study was undertaken to evaluate the combination of vinblastine (VLB) and DP in patients with advanced renal cell carcinoma and no prior chemotherapy. From August 1989 through December 1989, 15 patients with inoperable recurrent or metastatic renal cell carcinoma were treated with VLB 0.2 mg/kg (i.v. slow push) and concurrently received DP75 mg p.o. q.i.d. starting 48 hours before and continuing 48 hours after VLB administration. Courses were repeated every 3 weeks for a maximum of 8 weeks, or until disease progression or undue toxicities ensued. The predominant toxicities seen were mild neurotoxicity and leukopenia. Only 1 patient had grade IV leukopenia, and no lethal toxicities occurred. No objective responses were seen; 2 patients had stable disease for 29 and 30+ months. The median survival was 9 months (range: 2.5-30+). We conclude that at the dose and schedule used in this study, the combination of VLB and DP may be administered with acceptable toxicities, but is ineffective in the treatment of advanced renal cell carcinoma.

A phase II trial of interferon alpha-2A plus fluorouracil in advanced renal cell carcinoma. A Hoosier Oncology Group study.

In vitro studies have documented the synergistic activity of interferon (IFN) and fluorouracil (5-FU) in human cancer cell lines, and recent clinical trials have demonstrated the efficacy of this combination in metastatic colon cancer. The current study was undertaken to evaluate the combination of IFN alpha-2a plus 5-FU in previously untreated patients with metastatic renal cell carcinoma. From May 1990 through August 1990, 14 patients with metastatic renal cell carcinoma were treated with 5-FU 750 mg/m2/day continuous infusion IV days 1-5, followed by weekly IV infusions of 5-FU 750 mg/m2 beginning on day 12. Patients concurrently received IFN alpha-2a 9 x 10(6) IU subcutaneously 3 times per week beginning on day 1. The median age of patients treated was 57 (range 38-80) with a median Karnofsky performance status of 90 (range 60-100). Sites of metastases included lung only in 6 patients, liver only in 1 patient, 1 patient had bilateral disease at presentation, and the remaining patients had multiple sites of metastases. The median duration of therapy was 2 months. The predominant toxicities seen were stomatitis, nausea, flu-like symptoms and neurotoxicity. The only grade IV toxicity observed was severe vomiting in 1 patient, though 5 patients discontinued therapy within 2 months because of poor subjective response. With a minimum follow-up of 13 months no objective responses were seen. Thirteen of the 14 patients have had progressive disease and 11 have died. The median time to progression was 2 months (range 0.5-6 months) and the median survival was 5 months (range 2-14.5 + months).(ABSTRACT TRUNCATED AT 250 WORDS)

Etoposide, ifosfamide, and cisplatin in extensive small cell lung cancer.

From December 1987 through April 1989, 40 patients with extensive-stage small cell carcinoma of the lung were enrolled in a Hoosier Oncology Group (HOG) trial using etoposide, ifosfamide, and cisplatin (VIP). Patients with extensive disease were eligible if they had not received prior chemotherapy, had a Karnofsky performance status of 50 or more, and had adequate renal function (creatinine, less than 1.5 mg/dl) and bone marrow reserve (granulocyte count, greater than or equal to 2500/microliters; platelets, greater than or equal to 125,000/microliters). Doses of therapy were: etoposide 75 mg/m2/day on days 1 to 5, ifosfamide 1.2 g/m2/day on days 1 to 5, and cisplatin 20 mg/m2/day on days 1 to 5. The first 11 patients received a 5-day course; this was repeated every 21 days for four cycles, but therapy was shortened to 4 days when unacceptable toxicity was noticed in these patients. Overall, 14 (37%) had a complete remission (overall response rate, 71.1%) with a median survival of 42 weeks (28 weeks on 5-day regimen and 45 weeks on 4-day regimen). There were five early deaths. Although toxic, VIP produces a high complete remission rate in patients with extensive disease and warrants further evaluation. A prospective randomized trial comparing cisplatin and etoposide to the VIP regimen is underway through HOG.