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Overview of ifosfamide in small cell and non-small cell lung cancer Johnson DH. Division of Medical Oncology, Departmem of Medicine, Vanderbilt University Medical Center, Nashville. TN. Semin Oncol 1990;17:Suppl4:24-30.

The alkylating agent ifosfamide, an analogue of cyclophosphamide, has undergone extensive testing in the treatment of bronchogenic carcinoma. Available data indicate that ifosfamide as a single agent can affect a 50% objective response rate in small cell lung cancer (SCLC) and a 25% response rate in non-small cell lung cancer (NSCLC). With mesna uroprotection, the primary dose-limiting toxicity is myelosup- pression. In combination with other active agents, ifosfamide has yielded high response rates in both SCLC and NSCLC. Results of recent trials indicate that ifosfamide can be used safely in combination chemotherapy. Determination of the precise role of this agent in overall management of bronchogcnic carcinoma requires additional study, however.

Cisplatin, etoposide, and ifosfamide in non-small cell lung carci- noma. A phase II randomized study with cisplatin and etoposide as the control arm Paccagnella A, Favaretto A, Brandes A et al. Division of Medical Oncology, Padova General tfospital, U.L.S.S. 21, 35100 Padova. Cancer 1990;65:2631-4.

A Phase II randomized study testing the combination of cisplatin, etoposide, and ifosfamide (PEI) in non-small cell lung cancer (NSCLC) was performed. The standard combination of cisplatin and etoposide (PE) was used as the control arm. Since January 1987.78 patients were enrolled and then stratified for previous treatments and performance status (PS). The response rate (RR) of PEI was 26% (95% confidence limits[95 CL], 12% to40%), with onecomplete response (CR). TheRR ofPEwas26% (95 CL, 13% to39%), with noCR.Themedianresponse duration was 5 months (range, 2 to 13 months) for PEI and 4 months (range, 2 to 6 months) for PE. The median survival time was 6 months (range, I to 22+ months) for PEI and 7 months (range, 1 to 2l+ months) for PE. Leukopenia at recycling was similar in both arms (25% for PEI and 29% of PE). The median leukocyte nadir was 21OO/pI (range, 430 to 4870&l) for PEI patients and 3lSO/uI (range, 500 to SoOO/pI) for PE patients. Three patients had a drug-related death secondary to infec- tions. This Phase 11 randomized study suggested that the combination of cisplatinplusetoposideand ifosfamideproducesresults similartothose obtainable with cisplatin and etoposide.

Evaluation of high-dose etoposide combined with cisplatin for treating relapsed small cell lung cancer Masuda N, Fukuoka M, Matsui K et al. Deparmenf oflnlernal Medi- cine, Osaka Prefecwral Habikino Hospital, 3-7-I Hobikino, Habikino Osaka 583. Cancer 1990;65:263.540.

The synergism of combined high-dose etoposide with standard dose cisplatin (HD-EP) was evaluated in 20 patients who had relapsed after treatmenl of small cell lung cancer. Each patient was given etoposide at 500 mg/m*/day on days I to 3 and cisplatin at 80 mg/m’ (two patients given 120 mum*) on day I; autologous bone marrow was not trans- planted. Five patients were given recombinant human granulccyte colony-stimulating factor (rhG-CSF, SO @ml) in an attempt toreduce HD-EP induced neutropenia. The overall response was 50% (9 of IS); one complete response (6%) eight partial responses (44%). seven no change (39%). and two progressions of disease (11%). Of the 18 evaluable patients, 12 had been treated with regimens of conventional doses of etoposide with conventional doses of cisplatin or carboplatin, and of these, five (42%) achieved a partial response. The median duration of response was 8.4 weeks (range, 5.3 to 17.7) and the median survival time was 20.3 weeks (range, 1.6 to 91). All of the patients developed severe myelosuppression; rhG-CSF did not shorten the period of the leukopenia. Mucositis and liver dysfunction were the major nonhematologic manifestations of toxicity. Two treatment-re- lated deaths resulted from sepsis. These results suggest that the activi- ties of high doses etoposide with standard doses of cisplatin are synergistic against small cell lung cancer.

Chemotherapy for metastatic non-small-cell lung cancer. A case report Abratt RP, Willcox PA, Balding E, Hewitson RH. Department of Radiotherapy, Groove Schuur Hospital, Observarory 7925. S Afr Med J. 1990;77:161-2.

The role of chemotherapy for patients with metastatic non-small-cell lung carcinoma (NSCCL) is controversial A patient with intrathoracic metasmtic NSCCL, who was treated by moderate dose ctsplatin combi- nation chemotherapy and who remained clinically free of disease more than 5 years after presentation, is described. This treatment has not pre- viously been reported. A trial of moderate-dose cisplatin combination chemotherapy in selected patients with good performance status seems justified.

Phase II study of n-methylformamide (NSC 3051) and spiroger- mauium (NSC 192965) in the treatment of advanced small cell lung cancer Ettinger DS, Finkelstein DM, Abeloff MD et al. Departmenr of Oncol- ogy and Medicine, Johns Hopkins Oncology Center, 600 N. Wolfe Sweet, Baltimore, MD 21205. Invest New Drugs 1990;8:183-5.

Fifty-four evaluable patients with SCLC previously treated with chemotherapyreceivedeitherN-methylformamideorspiroge~anium. There was one partial response to N-methylformamide. The median survival times for patients treated with N-MFand spirogermanium were 11.7 and 12.6 weeks respectively. Five patients treated with N-MF ex- perienced severe toxicity while four patients treated with spiroger- manium experienced severe and life-threatening toxicity.

Teniposide (VMM) as second-line treatment for small cell lung cancer Tummarello D, Guidi F, Tortesi U, Dazzi C, Cellerino R. Clinica Oncologica, LlniversiladegliSludidiAncona, Ancona. AnticaocerRes 1990;10:397-9.

Twenty-six out of 53 patients with small cell lung cancer (SCLC) who relapsed or progressed following a first treatment (induction plus maintenance), were treated by a second-line chemotherapy consisting of: Teniposide (VM26). 60 mg/m2 i.v., days l-5, every 3 weeks until further progression. The response rate obtained in 24 evaluable patients was: 7 (29%) partial response, 4 (17%)minor response, 8 stable disease, 5 progressive disease and 2 patients with early death. In the whole group, median survival time from the start of VM26 treatment was 4

months (range. 1.11). These data were compared to the median survival (1 .S months, range l-7) of the remaining 27 patients, the control group, who at the time of progression did not receive further treatment. The difference between survivals was statistically significant (Log-rank test: p < 0.05). According to these data VM26 seemed to be active, but larger studies better focused on all clinical variables are needed before firm conclusions can be drawn.

Antagonistic effect of aclarubicin on the cytotoxicity of etoposide and 4’-(9-acridinylamino)methanesulfon-m-anisidide in human small cell lung cancer cell lines and on topoisomerase D-mediated DNA cleavage Jensen PB, Sorensen BS, Demant EJF et al. Depnrmenf of Oncology, The Finsen InslirutelRigshospiralef, 9 Blegdamsvej, DK-2100 Copen- hagen. Cancer Res 1990:50:331 l-6.

The effect of combinations of the anthracycline aclarubicin and the topoisomerase 11 targeting drugs 4’-demethylepipodophyllotoxin-9- (4,6-0-ethylidene-8-D-glue opyranoside) (VP-16) and 4’-(9s acridinylamino)methanesulfon -m-anisidide (m-AMSA) was investi- gated in a clonogenic assay. The cytotoxicity of VP-16 was almost completely antagonized by preincubating cells with nontoxic concen- trationsofaclaruhicin.Theinhibitionofcytotoxicity wasnotseen when the cells were exposed to aclarubicin after exposure to VP-16. The inhibition was significant over a wide range of aclaruhicin concentra- tions (3 nM to 0.4 pM), above which the toxicity of aclarubicin became apparent. A similar effect was seen on the toxicity of m-AMSA. In contrast to aclarubicin, preincubation with Adriamycin did not antago-