Abstracts/ Lung Cancer 11 (1994) 423-444 439

fails to provide definitive care, however, some practical guide lines call be planned to face the problem of how and when to treat relapsed small cell lung cancer patients.

Are we moving towards adinuow treabnent in small cell lung cancer (SCLC)? Zandwijk NV. Departmmtof Chest Oncology, i’he Netherlanu!v Cancer Institute, Plesmanlaan 121. 1066 CX Amsterdam. Aoticsncer Res 1994;14:B 309-11.

In the late sixties the first random&d placebo controlled study with cyclophosphnmide demonstrated improved survival in patients with extensive small cell lung cancer (SCLC). Since then chemotherapy has become the m&stay of treatment of SCLC A number of active combiition chemotherapy programs for SCLC were developed during the 1970s and early 1980s. Administration of three or four effective drugs simultaneously appeamd to be required for optimal results, but the particular regimen selected was of less importance than the delivery of doses that induced moderately severe but not life-threatening myelosuppression. The drugs chosen for a combination were justified on the basis of single agent activity, difference in mechanism of action and non-overlapping toxic effects. The actual doses were usually the resultoffeasibilitystudiesin whichthedosesofallexcept onedrug were held constant. Certain combinations becsme popular quickly, long before it wss appreciated that one of the drugs in the combination added more toxicity than benefit. It is therefore not surprising that the old concept that two drugs in combination are better thsn one, or three drugs in combination arebetter than two, is being increasingly criticized. There is recognition that at the time of diagnosis SCLC may already be partially resistant to multiple chemotherapeutic agents and that the strategy simulated by Goldiesnd Coldman may only partly he applicable to SCLC. Moreover, the development of hematopoietic growth factors has provided a reason to re-evsluate the doses of individual cytostatic agents in current combination regimes and to combine drugs that previously were thought to be incompatible. But even without growth factors, recent investigations with the single agent etoposide and the combination of etoposide and cisplatin have provided arguments against the old theories of ‘more is better’. Drug combinations must preferably be selected on the basis of phermacokinetic studies. Dose intensity has toberevisedandthscinatingopportunitieswillartiveassoonasefficient oral formulations of active drugs, such as platinum, ifosfamide and etoposide became available.

Smnll cell lung canker nnd topnlsnm- G&cone G. Dqartment of Ondogy, Free Uniwrsity Hospital, 1117 DeBodekaan. HVloBI Amstwukm. AnticancerRes 1994; 14:B 269-76.

Topoisomerasw are nuclear enzymes involved in steps of DNA metabolism which require topological modifications. Interestingly, theseedzymur&re been djscovered to be targets of several anticancer drugs in common cl&al w. Alterations of thetopoisomerase Sazy- have been described as associated with the development ‘of drug resistance to topoisomerase inhibitors. The best known alterations are reduced gene expression and mutations in the genes. The present knowledge of the role of topoisomemsw in lung cancer, and in small cell lung cancer in patticulu, is described here.

Art&d infusion cbenotharpy and embolization of bronchial arteryintbetreatmt2ntofluqcancer Yeog H-S. 3nl Clinkal Medical College, Bethune Medical University, Changdrun. Chin J Clin Oncol 1994;21: 110-2.

Twenty cases of lung csncer, including 14 small-cell carcinomas, 4

edeooauciaomPs and 2 ~~UUIIOW cell carcioomos were treated by arterial infusion chemotherapy and embolizntion of bronchial artery. There were 6 stage Il and 14 stage III cases in this gmup. Selective bronchial arteriography showed that all the 20 tumors were surrounded by fairly abundimt blood vessels. Inlirsion was performed via the bronchial artery supplying the tumor with dexamsthamne 2Omg and adrismycin40-5Omg followed by injection of mitomycin C 20 mg mixed with iodized oil (40%) l-3 ml immediately to embolixetheartery. Good results were achieved in all the cases.

A pilot study of combination cbcmotberapy for poor PS patients with small cell lung cancer Kudoh S, Morikewe T, Nukeriya N, Kobeyashi K, Yemede K, Hioo M et al. Fourth Dept. of Internal Medicine, Nippon Medical School. Nippon. Lung Cancer (Japan) 199&34:23-S.

Sixteen cases of small cell lung cancer (SCLC!) with poor prognosis were entered in a pilot study consisting of CDDP 30mglmz. VCR lmg/ body x 2deys. ADM 2Omglm’ACNU 3Omg/m* endMMC 3mglm’. All patients bed exteauive disease, snd their performance status (PS) was 3 or 4. Among 15 eligible patients, 1 complete and 1 I partial responses were obtained, resulting in an overall msponse rate of 75 % . Although the median survival time was 3.7 months, the PS improved in 10 patients. Toxicity levels wereacceptable, and no treatment-related death occurred. These results suggested that SCLC case with poor PS could improve their quality of life, using this combination chemotherapy.

ousbain-resisgntnon~neelllungceneereellliaeshowseollateral sensitivity to cisdiamminedichloroplatinum(H) (CDDP) Ohm& T, Nishio K, Ohm S, Kubota N, Ada&i M, Komiya K et al. Pharmacology Division, National Canm Rcscareh Institute. Tsukzyi S- 1-l. Chuo-ku, Tokyo 1W. Int. J Cancer 1994;57:1116.

We have reported that the cellular uptake of cisdiamminedichlor- oplstinum(11) (CDDP) was inhibited by an Na’,K*-adenosine triphos- phatase (ATPase) inhibitor, ouabain, in a human non-small-cell lung- cancer cell line, PC-14, but not in its CDDP-resistant cell line, PC-14/ CDDP. [‘H]Ouabain binding of PC-IYCDDP was about 50% lower than that of PC-14. Accordingly, we speculated that a decrease in Na*,K+-ATPaseactivityinPC-14/CDDPmightcontrituttetothedecrease in cellular CDDP accumulation. To clarify the relationship between the activityorexpmssionofNa’,K’-ATPasesndcellulsrCDDPaccumulation, we established an ouabain-resistant non-small-cell lung-cancer cell line (PC-14/OB300), which showed l.Bfold resistance to the cytotoxicity of ouabain. Interestingly, this cell line was 4.2-fold - sensitive to CDDP than PC-14. ‘Ihe accumulation of CDDP in PC-14/OB300 was increased to2.7-foldtbat inFC-14. ThiselevationofCDDPaccumulation was not considered to be caused by increased passive diflirsion, because the accumulation of CDDP in PC-14/OB300 was also inhibited by ouabain compared to PC-14. As one of the indices of Na’,K’-ATPase activity, we determined cellular =Rb+ influx rates. The uRRb’ influx rate was 15fold higher in PC-14/OB300 and fell to 0.7-fold in PC-14/ CDDP compared with PC-14. The mRNA expression of Na’,K- ATPsse was increased in PC-14/OB300 and decreased in PC-141 CDDP. There was no difference in cellular [W]ouabain biding between PC-14/OB3OOand PC-14. It is possible that Nn*,K’-ATPaseof PC-14/OB300 has a different afftnity for ouabain from that of PC-14. Our results suggest that the enyme. activity or the level of expression of Ns’,K’ATPase may contribute to the cellular uptake of CDDP and determine the sensitivity to CDDP.