338 Abstracts/Lung Cancel . 11 (1994) 323-344

first or second cycle. 12 Patients received P-100 with the first and 12 with thesecondcyclr. Foreach gmupcycleswithP-100werecompared to cycles without P-100. Resulrs: P-100 was well tolerated but no significant differencesbetween cycleswithand without P-lOOwere seen intheadministeredchemotherPpydose,depth~dduntionofneuttopenia, number of blood or platelet transfusions, WHO grade 3-4 infection or requirement for intravenous antibiotics. Of 24 evaluable patients 14 (58.3%) achieved CR and 4 (16.6%) PR. Patients achieving CR received radiotherapy. The median time to progression was 169 days (range 38-995 + days)and the median survival timewas 305 days (range 42-lO52+ days). Three patients are alive after 2 years (11.5%). 2 without relapse (7.7 96). Alopecia, nausea and vomiting occurred in all Patients but no treatment related deaths occurred. Concla.rion: In this study P-100 did not significantly influence the myelotoxicity associated with carlqrlatin-etoposide chemotherapy in the treatment of SCLC.

Treatment of non-small cell lung cancer: New cytostatic agents Sorensen JB. Department of Oncology, Rigshospiralet, 9 Blegdamsvej. DK-2100 Copenhagen. Lung Cancer (Ireland) 1993;lO: 173-87.

The literature on new cytostatic drugs in the treatment of non- small cell lung cancer and on new methods for administration of established drugs has been reviewed back to 1985. Two well-known cytostatic drugs, ifosfamide and etoposide, have been evahmted in trials using oral administration instead of the usual intravenous route, and a total of 26 new investigative drugs has also been evaluated. Oral administration of etoposide is associated with an accumulated response rate of I7 96 in four studies using a dose of 50 mg/mr daily for 2-3 weeks, followed by 1 week’s rest. Gral administration of ifosfamide yields an accumulated response rate of 18 R when the dose intensity is 7 g or more during a 4-week period. Among the new drugs tested, the most promising seem to be campthothecin-I 1, gemcitabine, vinorelbine, taxol. fotemustine, and mniplatin which have all shown response rates above2096amongpreviouslyuntreatedpaticn~. Also,theantimetabolites IO-EDAM and trimetrexate and the platinumanalogues carboplatin and (glycolate-O.0) diammine-platinum(B) are of interest, with cumulative response rates above 15% in previously untreated patients.

Suramin inhibits the phosphorylation and catalytic activity of DNA topoisomerase II in human lung cancer cells Funayama Y, Nishio K, Takeda Y, Kubota N. Ohira T, Ohmori T et al. Pharmacology Division, National Cancer Cenfer Research Inst, I-I Tsukiji 5-chome, Chuo-ku, Tokyo 104. Anticancer Rea 1993; 13: 1981- 8.

The impact of therapy with filgmstim (recombinant granulocyte colony-stimulating factor) on the health care cast associated with cancer chemotherapy Glaspy IA, Bleecker G, Crawford I, Staller R, Strauss M. UCU S&w1 of Medicine, Los Angeles, CA 90024-6956. Eur J Cancer Part A Gen Top 1993;29 (SuppI. 7):S23-S30.

Suramin is a prototype of a new class of anticancer drugs. We investigated the action of sunmin on the signal transduction pathways

The objective of the study was to estimate the net impact on hcalth resource utilisation of using recombinant gramdocyte colony-

to DNA topoisomemse II (Top0 II). Suramin showed a growth- inhibitory effect on a human lung cancer cell line (PC-9) with an IC, of

stimulatingfactor(Qrastim)foIlowingmyelosuppreasivechemotherapy. Cost minimisation of the study medication in a random&d. double-

about 160 g/ml. Suramin inhibited the catalytic activity of Topo II with blind, placebo-controIled clinical trial was conducted in teaching an IC, of about 100 g/ml without stabilization of the cleavable complex institutions and affiliated community hospitals participating in aclinical of DNA and Topo II. Suramin decreased the phosphorylation of Topo trial. 68 patients with small cell lung cancer undergoing II with an IC, of 175 g/ml but did not change the degree of Topo II expression. These IC, values for inhibition of catalytic activity and

cyclophosphamide, doxorubicin and etoposide chemotherapy were random&d to blinded placebo or filgrastim study medication at three

phosphorylation of Topo II were equivalent to the growth-inhibitory or 14 clinical trials sites. The patients received daily subcutaneous dose determined by tetrnzolium dye assay. Phosphotylation of the injections of tilgrastim or placebo, initiated 24 h afterchemotherapy and tyrosine residues ofTopo II was not changed by sunmin. In the presence ofokadaicacidapotent inhibitorofserinelthreonineprctein phosphatase

continued until the neutrophil count exceeded 10000 x 106/I after the time of the expected nadir. Differences in total charges, costs and

suramin also decreased the phosphorylation of Topo II suggesting that the drug did not act on the serinelthrwnine protein phosphatases

Medicare payments between treatment groups were the main outcomes measured. Compared to placebo patients, tilgrastim-treated patients had

inhibited by okadaic acid. Sunmin also inhibited the protein kinase C significantly fewer and less resource-intensive hospitahsations. After (PKC) activity of PC-9 cells. These results suggest that suramin accounting fortilgrastimpurchaseandadministration, thecharge model

decreases the phosphorylation of Topo II mediated by PKC. This effect of suramin might cause the inhibition of Topo II activity resulting in the growth inhibition of tumor cells.

Comparative study of theantitumor activity of bistramides A, D and Kagaimt a non-small cell bronch~pulmunary carcinoma Riou D, Roussakis C, Biard JF, Verhist JF. SMAB. 1 rue G Veil, 44035 Nonres Ceder. Anticancer Res 1993;13:2331-4.

Bistramides A D and K are substances extracted from the marine ascidian Lissoclinum bisttatum Sluiter that are capable of inducing in vitro terminal differentiation (GIDT) of cells from a non-small cell broncho-pulmonary carcinoma (NSCLCNJ hut present different in vitro toxicities. This study shows that only the least toxic bistramides D and K possess an antitumor activity. These two substances could be administered as a continuous treatment which would induce terminal differentiation of stem cells at their entry into the cell cycle thereby causing their destruction.

Combination therapy ofsmall cell lung cancer with teniposide, ifosfumide and carboplntin More D, Orfeuvre H, Nagy-Mignotte H, Mousseau M, Blanc-Jouvan F, Schaerer R et al. Service de Pneumologie, CHU A-Michalfon, BP 217X, 38043 Grenoble Cedu 9. Bull Cancer 1994;81:3842.

Thirty six SIC patients have been treated with a combination therapy of ifosfamide2g/mr, D I and D2, carboplatin 300 mglm’ D 1 and teniposide 100 mglm’ DI to D3. All patients were younger than 70 years, 3 1 males, live females, ten limited diseases, 26 extended diseases (without brain metastasis) perfomance status 0. 1 or 2, mean weight loss 3.7 kg. Thirty six patients were evaluable for response. We have noted three complete response and 28 partial response (objective response rate 86%). The main toxicity of this combination therapy was myelosuppression (86% of grade 3 and 4). Twenty seven patients have relapsed, the median relapse free survival time is 310 days. The median survival of the 36 patients is 340 days, one patient is alive more than 30 months after the diagnosis. The ifosfamide-carboplatin-teniposide combination is an effective treatment in small cell lung cancer, its toxicity remains tolerable.