140 Abswacts/Lung Cancer I1 (lW4) 123-150

antagonists at the same effective concentrations as in small cell lug carcinoma cells. omega-conotoxin and omega-agatoxin IVA, which blocktheN-and P-typechannel respectively, hadnoeffect onGLC8 cell proliferation. It is concluded that the presence of extracelhdar Ca*+ is a positive stimulus for small cell lung carcinoma cell growth. However, under our experimental conditions, the calcium chamtel blockers inhibited DNA synthesis most probably by a mechanism other than VDCC antagonism.

CVM versus ACE in the treatment of small cell lung cancer Jones AL, Holbom J, Ashley S, Smith IE. Royal Marsden Hospiral, DownsRoad, Surfon, SurreyS1U25PT. Gncology(Switzerland) 1993;SO Suppl2: 10-S.

In an attempt to s&eve adequate palliation in patients with small cell lung cancer (SCLC) while keeping toxicity to a minimum, we compared CVM (carboplatin/vinblastinestinelmethotrexate) and standard therapy with ACE (doxombici&yclophosphamide/etoposide). None of the 104 SCLC patients with limited or extive disease. who participatedhedreceivfdprevioustmatmmt. ABerstratification~ to disease extent, patients were randomized to receive either CVM or ACE. The maximum number of chemotherapy course8 was six. When response rates were compared, ACE was found to be somewhat superior to CVM in terms of objective response [CVM 67 96.95 % confidence interval (CI) 54-7996; ACE gg%, 95% CI go-97%; p = 0.061; however, a significant difference. was evident only among extensive- disease patients. Median response durations (CVM 6 months, 95% CI 5-8; ACE 5 months, 95% CI 3-6) and median survival times (CVM 8 months, 95 96 CI 7-10, ACE 7 months, 95 46 CI 4-9) were comparable. CVM met the goal of producing significantly less hematologic toxicity than occurred with ACE. Leukopenia affected 92% of ACE-treated patients and 48 96 of CVM-treated patients @ = O.OOS), and was severe in 80% of the ACE group and 20% of the CVM group. Alopecia occurred much more frequently among those treated with ACE (91 vs. 24%; p < O.OOl), as did infection (59 vs. 24%; p C 0.001). The selection of a specific chemotherapy regimen must be individualized. CVM may be appropriate for patients in whom intensive chemotherapy is contraindicated due to performance status, age, concomitant medical disease, or patient refusal.

Interferon therapy in lung cancer Pohl WB. II. Medizinischc Abteilung. Whebninenspi~al, Montlean- strawe 37, A-1160 Wien. Wien Med Wochenschr 1993;143:450-5.

The constant increase of lung cancer incidence is confronted with the relatively low efficacy of drug therapy in patients with advanced stages of this disease. Accordmg to results of phase II studies interferon-a (IFN-a) monotherapy used as palliative measure is ineffective in alI histological types of lung cancer. However, in certain therapy settings 1FN-a has some efficacy. In small ccl lung cancer IFNa therapy, when given as mainteaance following chemo- and/or radiation therapy- induced remissions, has shown some clinical benefit as documented by a prolongation of remission-free intervals. In patients with advanced non-small cell lung cancer and especially of the squamous cell type the combination of IFNa with cisplatinum achieved remissions in about 45 96. The efficacy of IocoregionaI administration, i.e. intrapleural. in patients with malignant effusions is currently under investigation.

Dose-dependent interleukind stimulation of thrombopoiesis and ne-utropoiesis in pa&nts with small-cell lung carcinoma before and following chemotherapy: A placeJwcontrolled randomized phase Ib study D’Hondt V, Weynants P, Humblet Y, Guillaume T, Canon J-L, Beauduin M et al. Oncology Unit, Catholic University oflouvain, UCL

54.71.54AwnueHippocrate. 1ux)Rrwsels. JClinGncol I993;I 1:2063- 71.

Purpose: TO evaluate the safety, tolerance, and hematologic effects of recombinant human interleukin-3 (IL-3) in patients with sma~I_cell lung cancer (SCLC) before and following multiagent antineoplastic therapyinaplacebocon trolled, randomized, double-blindstudy. Patients and M&o& Tweaty-eight patients (22 men and six women; median age, 60 years) with previously untreated SCLC entered the study. Patients were assigned to six groups of escalating-dose IL-3 ranging from 0.25 to 10 g/kg/d administered by continuous infusion for 7 days, with one patient in each group receiving placebo. After a I-week interval, the first of three cycles of carboplatin, etoposide (VP16), and epirubicin (CVE) given every 3 weeks was administered. The second cycle of CVE was followed by 7 days of IL-3 administered at the same daily dose as administered during the first infusion. Results: The maximum-tolerated dose was not encountered in this study. Fever was the most frequently observed side effect. Before any chemotherapy, World Health Organization (WHO) grade II fever only appeared at doses 2.5 g/kg/d. Gther side effects included rash, headache, and myalgia. During the first infusion of IL-3, before administration of chemotherapy, dosedepeadent incr&?s in peripheral-platelet counts (r = .613; P < .OOl) and neutrophil counts (r = SOS; P = .007) were observed. Following the second cycle of CVE, recovery of peripheral platelet counts was faster as compared with the first cycle of CVE for patients treatedwith 7.5 and log/kg ofIL-3 (P = .021). Chemotherapy postponements due to myelotoxicity were also less frequent following the second cycle of CVE as compared with the first for patients treated with 2.5 g/kg of IL-3 (P = .036). Compared with an age-matched historical group receiving identical chemotherapy (n = 191), administration of IL-3 did not modify either disease-free survival or overall patient survival rates. Conclusion: IL-3 is well tolerated at doses up to 10 g/kg/d. In the absence of qhemotherapy, biologic effects on both neutrophils and platelets were seen at doses 2.5 g/kg/d. IL-3 infusion following the second cycle of CVE appears to reduce chemotherapy-induced myelosuppreasion, but doea not alter tumor response or patient survival rates.

Cis-diamminedichloroplatnium(I1) inhibits p34(cdc2) protein kinase in human lung-cancer cells Nishio K. Fujiwam Y. Miyahara Y. Take& Y. Ohim T. Kubota N et al. Pharmacology Division, National Cancer Center Research Inst. Tsukiji 5-1-1, Chuo-ku, Tokyo 104. Jnt J Cancer 1993;55:616-22.

cis-Diamminedichlomplatinum(II) (CDDP) induced $-phase-t in PC-9 human cancer cells. To elucidate how CDDP acts on c&cycle regulation, we analyzed the effect of CDDP on cell-cycle regulators such as p34(cdc2) protein kinase. p34(cdc2) protein kinase activity was maximuminG,phaseanddecreasedaRerG,IMtraasitioninsynchronited PC-9 human lung cancer cells. Evidence for a phosphorylated p34(cdc2) protein k&se. complexed with cyclin B was obtained from cells in G, phase and thep34(cdc2) protein w appeared to be dephosphorylated at M phase. Aftor exposure to CDDP in G, phase, PC-9 cells were arrested in G, phase. The activation of p34(cdc2) pmtein kinase was inhibited by CDDP. Cyclin A and wee-l kinase were not affected by the exposure to CDDP. Cyclin B was degraded in M phase in PC-9 ce,Us. Exposure to CDDP did not affect the degradation of cyclin B. Our data suggest that the effect of CDDP on cell-cycle phase might be regulated by the dephosphorylation of p34(cdc2) protein kinase. To determine whether the p34(cdc2) protein kinase is a primary target for CDDP, we examined the direct effect of CDDP on tyrosine dephosphorylation of p34(cdc2) protein kinase in cellular extracts. Cell IysateS from synchronized PC-9 in G2 phase were immunoprccipitated with pI3- Sepharose beads. In vitro dephosphorylation of phosphotymsine of p34(cdc2) protein kinase was observed after exposure to okadaic acid in