A randomized Phase II study of interleukin-2 with and without beta-interferon for patients with advanced non-small cell lung cancer: an Eastern Cooperative Oncology Group study (PZ586).

Interleukin-2 (IL-2) and beta-interferon (beta-IFN) are biologic agents with antitumor activity observed in preclinical models. Some studies of patients with advanced non-small cell lung cancer treated with IL-2 report relatively long survival, despite low response rates. Seventy-six evaluable patients with stage IV non-small cell lung cancer were treated in a randomized Phase II study with either IL-2 alone or IL-2 plus beta-IFN. Patients received either IL-2 at 6 x 10(6) Cetus units/m2 3 days weekly or the combination of IL-2 at 5 x 10(6) Cetus units/m2 plus beta-IFN at 6 x 10(6) units/m2, both given 3 days weekly. Both biologic agents were administered by intravenous bolus injection on an outpatient basis. Objective responses were observed in 3/76 (4%)) patients. Grade 4 toxicity occurred in 3/39 patients treated with IL-2 alone, and in 4/37 patients treated with IL-2 plus beta-IFN. An additional lethal respiratory toxicity occurred in a patient who received IL-2 plus beta-IFN. The median survival of all patients treated on this study was 33 weeks. Despite producing only a 4% objective response rate. IL-2 appears to have a favorable impact on survival comparable to chemotherapy. The role for this immune therapy in the management of non-small cell lung cancer requires further study.

Phase II study of patients with metastatic nonsmall cell carcinoma of the lung treated with paclitaxel by 3-hour infusion.

BACKGROUND: Single-agent chemotherapy produces partial responses in the range of 7-27% in patients with Stage IV nonsmall cell lung carcinoma (NSCLC). Cisplatin-based combination regimens have achieved higher response rates but with significant toxicity. Two prior studies employing 24-hour infusions of paclitaxel showed responses of 21% and 24%. The purpose of this Phase II study was to determine the effects of paclitaxel administered by short duration infusions on response rate, toxicity, and quality of life (QOL) in patients with NSCLC. METHODS: Twenty patients with histologically proven Stage IV NSCLC were enrolled in this study. All were treated on an outpatient basis with standard premedication followed by paclitaxel 200 mg/m2 infused intravenously over 3 hours. Treatments were repeated every 21 days for a maximum of 6 cycles. RESULTS: The objective response rate was 6/19 (32%; 95% confidence interval, 13-57%). The median duration of response was 6.0 months (range, 2-13 months). The median survival of the entire group was 6.0 months (range, 2-24+ months), and the 1-year survival rate was 22%. Toxicity was mild, with only one hospitalization required for treatment of catheter-related thrombosis. Nonresponding patients were found to have worsening Functional Assessment of Cancer Therapy (FACT)-G and FACT-L scores. Because this was a small clinical study, it did not demonstrate consistent improvement in FACT-G or FACT-L in responding patients. CONCLUSIONS: Paclitaxel given as a 3-hour infusion is a well-tolerated, active single agent in the treatment of Stage IV NSCLC, worthy of further study. Baseline QOL scores predicted those more likely to respond to treatment, but changes in QOL status did not correlate well with objective response status.

Development of anemia and recovery in prostate cancer patients treated with combined androgen blockade and radiotherapy.

BACKGROUND: The objective of this study was to document previously unreported anemia in prostate cancer patients treated with neoadjuvant combined androgen blockade (CAB) and pelvic radiotherapy (XRT). METHODS: Four institutions treated 141 patients (mean age +/- SD, 70.9 +/- 6.5 years) with zoladex 3.6 mg injection subcutaneous depot monthly and flutamide 250 mg orally three times per day for 2 months (CAB), followed by zoladex and flutamide with concurrent XRT (65-70 Gy) for 7-8 weeks. RESULTS: After the XRT, the patients were randomized to receive no further treatment (Z- group, 71 patients) or zoladex alone (Z+ group, 70 patients) for 2 years. Hemoglobin (Hb) levels decreased > or = 1 g/dl (mean +/- SE, 2.1 +/- 0.1 g/dl) in 98/131 patients (75%) after 2 months of CAB, and > or = 2 g/dl (3.1 +/- 0.1 g/dl; range, 0.1-6.8 g/dl) in 106/131 patients (81%) after an additional 2 months of CAB with concurrent XRT. The decrease in Hb levels paralleled the decreased in testosterone levels. No evidence of blood loss or hemolysis was found. CONCLUSIONS: There was no association between incidence or rate of Hb decrease and race, age, or pretreatment prostate-specific antigen (PSA) levels. However, the recovery from anemia after completion of CAB in African-Americans was slower than in Whites in the Z+ group (P < 0.04). Whereas grade 1 hematologic toxicity may occur in < 5% of the patients with zoladex alone, and approximately 6% with flutamide alone, in our study 81% showed mild to pronounced anemia. Since anemia has not been observed after treatment with XRT alone or XRT followed by zoladex, we conclude that the anemia was due to CAB. Recognition of this side effect should avoid unnecessary diagnostic evaluations.

Protracted intravenous fluorouracil infusion with radiation therapy in the management of localized pancreaticobiliary carcinoma: a phase I Eastern Cooperative Oncology Group Trial.

PURPOSE: The purpose of this study was to determine the maximum-tolerated dose (MTD) of fluorouracil (5-FU) administered as a protracted intravenous (IV) infusion with concurrent radiation in patients with pancreaticobiliary carcinoma. METHODS: Twenty-five patients with recurrent, residual, or unresectable carcinoma of the pancreas or biliary tract were treated on a phase I trial of protracted IV infusions of 5-FU, beginning at 200 mg/m2/d, concurrent with radiation therapy (59.4 Gy in 33 fractions over 6 to 7 weeks). Chemotherapy began on the first day of radiation and continued through the entire course of treatment. After each cohort of five patients had been treated and observed, the daily dose was escalated in 25-mg/m2 increments until dose-limiting toxicity was encountered. An additional cohort of five patients was treated at the MTD. Clinical examination and computed tomography (CT) were used to evaluate response and patterns of progression. RESULTS: The MTD of 5-FU was 250 mg/m2/d. The dose-limiting toxicity was oral mucositis. The median survival duration of all patients treated was 11.9 months and the 2-year survival rate was 19%. Eleven of 25 patients remain free of local progression and four patients are without evidence of progression at 18+, 18+, 34+, and 44+ months following treatment. CONCLUSION: Concurrent radiation with protracted 5-FU infusion at 250 mg/m2/d is well tolerated and shows evidence of activity against tumors of the pancreas and biliary system.

Second malignant neoplasms complicating Hodgkin's disease: the National Cancer Institute experience.

The medical records of all patients treated for Hodgkin's disease during the years 1964-1981 were reviewed. Four hundred seventy-three previously untreated patients were analyzed. Thirty-four subsequent second malignant neoplasms were observed in 33 patients among those treated for Hodgkin's disease. Eight cases of acute nonlymphocyctic leukemia, one case of chronic myeloid leukemia, three cases of non-Hodgkin's lymphoma, three cases of sarcoma, and 19 other tumors were identified. The ten-year estimated risk of leukemia by treatment was the following: radiotherapy only (0), chemotherapy only (0.02), initial combined radiotherapy-chemotherapy (0.06), and salvage combined radiotherapy-chemotherapy (0.09). The ten-year estimated risk of solid tumors was 0.07 overall, with all treatment groups associated with similar risks. Unlike some other reports, a greater risk of leukemia in patients who began treatment for Hodgkin's disease at age 40 or older was not found. However, a positive association was noted between increasing risk of solid tumors and increasing patient age.

"Salvage" radiation therapy for intrathoracic small cell carcinoma of the lung progressing on combination chemotherapy.

Thirty-two patients with small cell carcinoma of the lung were given chest radiotherapy to progressive intrathoracic tumor after failing chemotherapy. Two-thirds of these patients received split-course treatment at a dose of 4000 rad in 10 fractions. Sixteen of 25 evaluable patients (64%) had an objective response, but only five responders did not progress within the port during life. Median time to local progression was 16 weeks. Two patients, one of whom was given concurrent chemotherapy, survived greater than 18 months, and one is free of disease at 31+ months. Short-term palliation of chest disease and occasional long-term survival are possible with this regimen, although most patients will die with systemic disease within several months. Small cell carcinoma of the lung is less responsive to irradiation as second-line therapy than as initial therapy, but doses of greater than or equal to 4000 rad can offer symptomatic relief in many cases and, rarely, survival beyond 18 months.

Evaluation of weekly escalating doses of dichloromethotrexate in patients with hepatocellular carcinoma and other solid tumors.

Twenty-one patients with solid tumors were treated with weekly 6-h intravenous infusions of dichloromethotrexate (DCM), with escalating doses every other week. Frequently observed toxicities included leukopenia, thrombocytopenia, and mucositis. Nausea, vomiting, diarrhea, and elevation of hepatic enzymes and bilirubin occurred less often. The toxicity of DCM was dose-dependent; the maximum tolerated dosage excalation plan was 400 mg/m2 x 2 weeks, 800 mg/m2 x 2 weeks, and then 1,200 mg/m2 weekly. Plasma concentrations of DCM were measured during 61 infusions and apparent half-lives determined. The plasma elimination of DCM appears to be similar to that of methotrexate. Three objective tumor responses seen in the seven hepatocellular carcinoma patients treated warrant further investigation.