152 Abstracts/Lung Cancer 12 (1995) 113-160

Subcutaneous heparin treatment incises survival in small cell hmg cancer Lebeau B, Chastang C, Brechot J-M, Capron F, Dautzenberg B, Delaisements C. Service de Pneumologie, Hopital Saint-Antoine, 184 rue du Faubourg Saint-Antoine, 75012 Paris. Cancer 1994;74:38-45. Background. A positive influence of anticoagulant treatment in small cell lung cancer (SCLC) has been suggested by experimental and clinical data. Methods. In a multicenter clinical trial, 277 patients with SCLC were randomized either to receive or not to receive subcutaneous heparin injections for 5 weeks at effective doses, which were monitored by blood coagulation tests. All patients received one of the two chemotherapy regimens studied in this trial, for eight courses in the case of patients with complete or partial response, and subsequently were randomized to receive delayed thoracic radiotherapy alter these eight courses. Results. In comparison to the 139 patients who did not receive heparin, the 138 patients who received anticoagulant treatment obtained better complete response rates (37% vs. 23%. P = 0.004), better median stival (3 17 days vs. 261 days, P = 0.01). and better survival rates at 1, 2, and 3 years (40% vs. 30% 11% vs. 9% and 9% vs. 6% respectively). At subgroups analysis, the results on survival were obtained for limited forms (F = 0.03) but not for extensive diseases (I’= 0.3 1). No important bleeding or thrombocytopenia was related to heparin treatment. Conclusions. These results confirm the value of anticoagulant treatment in SCLC, already suspected for warfarin and now proven for heparin, but the modes of administration and the biologic explanations for this activity still warrant further investigation.

Effects of grarmlocyte-macrophage colony-stimulating factor and interleukin-3 on small cell lung cancer cells Pedrazzoli P, Bacciocchi G, Bergamaschi G, Cazzola M, Danova M, Gibelli N et al. Divisione di Oncologia Medica, Fondazione Clinico del Lavom, Ma Boezio 26, 27100 Pavia. Cancer Invest 1994; 12:283-g. Nonhematopoietic malignant cells may express receptors for hemato- poietic growth factors and respond to these peptides. The aim of the present study was to investigate whether small cell lung cancer (SCLC) cells may he stimulated to proliferate by hematopoietic growth factors such as gramdcqte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 @L-3), which are currently used in clinical trials in combination with cytotoxic chemotherapy. We studied two SCLC cell lines, H69 and N4 17. The effects of GM-CSF and IL-3 were evaluated by studying clonal growth, ‘H- thymidine incorporation, BUDWDNA bivariate flow cytometry, c-myc and N-myc onwgene expression, and myeloid surface markers. Our experiments show that both GM-CSF and IL-3 can increase ‘H-thymidine incorporation and cloning efficiency and reduce DNA synthesis time of H69 and, to a lesser extent, N417 cells, supporting the hypothesis that hematopoietic growth factors can stimulate the growth of some malignant nonhematopoietic cells in vitro. Further in vitro and in viva studies are needed to determine whether clinical trials applying these factors for bone marrow recovery after chemotherapy of solid tumors may be hazardous by potentially stimulating growth of remaining tumor tissue.

darly Phase JJ clinieal study of KW-2307 in patients with lung cancer Furuse K, Ohta M, Fnkuoka M, Knrita Y, Kobayashi K, Hasegawa K et al. Department of Internal Medicine, National Sanatorium, Kinki Central Hospital, Higashi, Osaka.. Jpn J Cancer Chemother 1994;21:785-93. A multicenter early Phase II clinical study of KW-2307, a new vinca alkaloid derivative, in patients (pts) with lung cancer was conducted in 15 hospitals. Ninety-seven pts were enrolled, among whom 95 were eligible. Seventy of the eligible pts had non-small cell cancer (NSCLC)

and 25 bad small cell cancer (SCLC). PR was obtained in 13 (18.6%) of NSCLC pts and 3 (12%) of SCLC pts. Only those who had no previous chemotherapy showed PR in NSCLC pts, and the response rate in these pts was 29.5% (13144). As to the correlation between dosage and tumor effect, a better effect was exhibited at higher doses, with response rates of 21.7% (5/23) and 38.1% (8/21) at 20 mglm’ and 25 mg/mz, respectively. The major adverse effect of this drug was leukopenia (neutropenia), which was Grade 3 or 4 in many cases. Recovery from this complication, however, was rapid. Other adverse effects included mild hepatic dysfunction, anorexia, nausea/vomiting, fever, general fatigue, phlebitis and constipation. The incidence of peripheral nervous disorder such as the paresthesia axnmonly okrved with tinca alkaloids, was as low as 10%. and the symptoms, if any, were mild.

Carboplatin combined etoposide in the treatment of lung cancer Su D-H. Department o/Medicine, Jiangxi Tumor Hospital, Jiangxi. Chin J Clin Oncol 1994;21:196-8. Sixty-four patients with lung cancer were treated with carboplatin (350- 420 mg/m*) combined with etoposide (100 mg x 5 days) for more than two courses. The overall response rate (CR + PR) was 40.6%. The response rates for 25 small cell lung cancer patients and 30 non-small cell lung cancer patients were 80% and 15% respectively. The vital toxicity was myelosuppression, and the alimentary toxicity and nephrotoxicity were mild.

Phase II study of docetaxel for recurrent or metsstatic non-smail- cell lung cancer Fossella FV, Jin Soo Lee, Murphy WK, Lippman SM. Calayag M, Pang A et al. DTHNMO, Texas Univ. M.D. Anderson Can. Ch., Box80, ISIS Holcombe Blvd, Houston, TX 77030. J Clin Oncol 1994;12:1238-44. Purpose: We conducted a phase II study to determine the response and toxicity of docetaxel (Taxotere; Rhone-Poulenc Rorer Pharmaceuticals, Inc. Collegeville, PA) in chemotherapy-naive patients with advanced non-small- cell lung cancer. Patients and Methods: We treated 41 chemotherapy-naive patients who had stage IIlb or IV non-small-cell lung cancer with 100 m&n2 of docetaxel intravenously over 1 hour every 3 weeks. Reqxmses were assessed after every one to two treatment wurses. Responses of 39 of 41 patients were assessable. The patients’ median age was 63 years; 90% of patients had a Zubrod performance status of 0 or 1. The predominant histology was adenocarcinorna (54%). and 90% of patients had stage IV disease. Results: Thirteen patients (33%) achieved a partial response to treatment, and the median response duration was 14 weeks. Grade 3 or 4 neutropenia occurred in 97% of patients; this was usually of brief duration and was associated with serious infection in 17% of patients. Other acute toxic effects included easily trcatcd hypersensitivity reactions (36% of patients) and dermatitis (74%). We also observed fluid retention (with peripheral edema or pleural effusion or both) in 54% of patients. This was a cumulative side effect that generally occurred late in treatment. Conclusion: Docetaxel administered at 100 mg/m’ intravenously every 3 weeks has significant activity against non- small-cell lung cancer, with a 33% major response rate. Primary toxicities were neutropenia, hypersensitivity, and fluid retention.

Phase II trial of docetaxel in patients with stage III and lV non- small- cell luog cancer Francis PA, Rigas JR, Kris MG, Pisters KMW, Orazem JP, Woolley KJ et al. Memorial Sloan-Kettering Cancer Cti. 1275 YorkAve, New York, NY 10021. J Clin Onwl 1994;12:1232-7. Purpose: This phase II study was conducted to evaluate the efficacy and toxicity of do&axe1 in the treatment of patients with advanced non-