Abstracts /Lung Cancer 12 (199s) 265-329

overall survival of 5 months. Besides alopecia, myelosuppression was the most significant drug-related toxicity. Observed side effects in 59 cycles of chemotherapy were granulceytopenia (<I ,OOO/il) tn 23% of the treatment cycles, thrombocytopenia (<75,OoO/il) in 25%, anemia (<IO g/dl) in 64%, and nausea- vomiting (grades 2) in 8%. Mild renal insuffIciency (serum creatinine, I S-2 1 mg/dl) occurred in six patients. Three toxic deaths were observed during or immediately after cycle I, and were related to granulocytopaia. We conclude that this regimen has modest activity in advanced NSCLC; but this therapeutic approach does not appear to produce a major improvement in the treatment of this disease. Thus, in advanced NSCLC, continued evaluation of new chemotherapeutic agents should remain the major emphasis of investigational therapy.

Competikinhibitioa bygenisteioand ATPdepmdmceofdPuaorubih transport in intact MRP overexpressing bumaa small cell lung cancer cells Versantvoort CHM, Broxtcrman HJ, Lankclma J, Feller N, Pine& HM. De- parbnenf o/Medical Oncolo~, Free Universi@ Hospital. De Boelelaan III 7. 1081 m Amslerdam. Biochcm Phamwwl 1994;48:1129-36.

In several multidrug resistant tumor cell lines without overexpresston of P- glycopmtein (non-Pgp MDR), a decreased accumulation of drugs has been shown to contribute to resistance. We have recently reported that daunombicin (DNR) accumulation was decreased in the multidrug resistance-associated protein overexpressing GLC4IADR non-Pgp MDR small cell lung cancer cell line due to an enhanced energy-dependent elllux whrch could be inhibited by the isoflavonoid genistein. The purpose of this work was I-fold: (i) to investigate the mechanism by which genistein inhibits the DNR efflux in the GLC41ADR cells; and (ii) to characterize the dependence of DNR transport on ATP concen- tration in intact GLC4/ADR cells. The active transport of DNR in GLC4IADR cells appeared to be a saturable process with an apparent K(m) of DNR of 1 4 i 0.4 iM. Genistcin increased the apparent K(m) value of DNR, suggesting that this agent is a competitive inhibitor of DNR transport. These data provide additional evidence that energydependent DNR transport in GLC4IADR cells is a protein-mediated process. In addition, genistein decreased cellular ATP concentration in a dose-dependent manner in sensitive as well as in resistant cells. Marked inhibition of DNR transport activity in intact GLC4IADR cells was found when cellular ATP concentration was decreased below 2 mM by sodrum &de or 2-deoxy-D-glucose. Thus, since DNR transport in intact GLWI ADR is already inhibited at modest cellular ATP depletion, a limitation in ATP supply might open ways to make MDR cells more susceptible to drug toxicity

Radiotherapy

Palliative eodobronchial bracbytherapy for central lung tumors: A prwpective, randomized comparison oftwo fractionation schedules Huber RM, Fischer R, Hsutmann H, Pollinger B. Wendt T, Muller-Wening D et al. Medizinische K/in&, Klinikum Innenstad~ LudwigMaximilians Universifaf, Ziemssensfrasre I. D-80336 Munchen. Chest 1995;107:463-70.

Aim o/f/r.? shrdy: Remote high dose rate brachytherapy is an effective local treatment modality for central lung tumors and has the potential to improve survival time. Optimal dose and fractionation schemes have not been identified yet. We conducted a prospective randomized study to compare two treatment schedules in terms of survival time, local tumor control, and possible complications. Design: Group I received 4 brachythcrapies with a dose of 3.8 Gy (at a IO-mm depth) on a weekly basis, and group 2 received 2 treatments with 7.2 Gy (at a IO- mm deplh) at a 3-week interval. At .a depth of 5 mm, the calculated doses would be 8 and 15 Gy. This study is still ongoing. Here we report interim results. P&en& Ninety-three patients with advanced cancer were included in the study, 44 were in group 1 and 49, in group 2. Both groups were comparable regarding age, sex, tumor stage, Kamofsky performance status, and histologic findings. Interventions: A mean total irradiation dose of 13.4 f 5.2 Gy for group I and 13.7 i 4.4 for group 2 were applied (calculated at IO mm from the source axis, equivalent to 27.9 Gy in group 1 and 28.5 Gy in group 2 at a 5-mm depth). Resulfs: The l-year survival rate was 11.4% in group I and 20.4% in group 2. No significant differera in survival time was found, but mean survival was longer m group 2 (49 weeks) than in group 1 (26 weeks). Local control after 3 months was

comparable m both groups. Fatal hemoptysis occurred at a similar rate in group 1 (22.2%) and in group 2 (21.1%). Conclusion: High-dose rate brachytherapy with 2x7.2 Gy with a 3-week interval is equivalent to a 4x3.8- Gy regimen on a weekly basis. The shorter treatment schedule is more convenient for patients, does not cause more side effects, and provides an equal local tumor control.

Comparative aswssment of three radiotherapy treatment protocols for inoperable cerebral metsstases of non-small cell lung carcinoma Demange L, Franks A, Panis X. Jr&&r Jerm-Godinof, Rue du General Koenig, 51056Reims Cedex Radio1 Oncol 1994;28:178-82.

Radiotherapy iso& suggested in the treatment ofinoperable brain metestases ofnon small cell lung carcinoma. This retrospective study of 83 cases has enabled us to assess the survival of irradiated and not irradiated patients as well as the predictive factors of better outcome from treatment. Protocols delivering 30 Gyl IOf/lSd and 36 Gy/6025d lead to a significantly longer survival than the one delivering 20 Gy/SffSd (p < O,ooOS). A Good initial neurological status and the improvement of neurological signs alter radiotherapy are two factors of favourable prognosis. However, time of onset of metastasis, histology, existence and number of extracerebral metastases have no influence on survival. We conclude that metastaszs must be irradiated early, as scan BS the first neurologacal dwxders appear. Treatment by irradiation of advanced metastases inducing maJor neurological disorders must be compared with the use of corticosteroids alone. Finally, we recommend the use of a dose greater than 20 GylSfiSd. with a fractionation adapted to the patient’s neurological status

IntrPLwiarlirradiadoni~~the~atd~aotainvayubstmcdoo Kohck PH. Pakisch B. Glaruer H. Auenbruggerplatr 36. A-8036 Gras. Eur J Surg Oncol 1994;20:674-80.

A group of 79 patients with non-resectable lung carcinomas (Tl, I, T2, 13: T3.34, T4,19; recurrence, 12) underwent endobronchisl iridium-192 highdose- rate aRerlo.sding therapy (5 Gy/session total dose: 5-25 Gy. mean 11 6 Gy). In 39 cases the fair general condition and absence of mctastases allowed cxtemal- beam irradiation (EBR) to be administered (50-70 Gy total dose; Zgy/day), starting 1 week a&r the brachythcrapy session. In nine cases with superior vena cave syndrome, EBR (30 Gy total dose; 3 Gy/dsy) was administered concomitantly. Improvement in symptoms of respiratory obstruction was noted in 87% of our patients The mean duration of palliation was 17.1 weeks m the group without and 34 7 weeks in that with additional EBR. The median survival time was 6 months without and I3 months with additional EBR In T4 cases EBR had no impact on the l-year survival (30.8% vs 24.4%. P > 0.05) The rate of severe complications was 7%. without significant differences behveen cases with or without EBR.

Met-national mwey of radiotherapy practice for radical treatment of non-small cell lung cancer Van Houne P, Gregor A, Philips P. Department o/Rad;orheropy. h~t~r~r J&S Border. Heger Dorder Srreer I-1000, Bnrsre/s. Lung Cancer (Ireland) I 994; l I: Suppl 3:Sl29-38.

This postal survey was designed to assess the possible agreement or differences in staging, selection criteria and radiation volumes for a curative treatment ofnon- small cell lung cancer. The questionnaire was sent to 263 radiotherapists from 38 drfferent countrtes; 1 I4 responses (43%) were received. In this sample, some geographical differences, mainly for staging procedures (the we of brain CT scan Or bone scan) and selection criteria (the role of positive mediastinal lymph nodes), were an. There WBS a good agreement behwen radiotherapists in the choace of treatment volumes in the five different clinical scenarms. The chn~l and radiobiological findings of the last decade have dixredrted the routine use of spht course or hypofractionation schedules. Further studies are needed to improve the technical basis of thoracic radiotherapy.

Tkeedhensional conformal radiotherapy ia bnmcbogenic carcinoma: Considerations for implementation Emami B, Graham MV, Purdy JA. Radialion Oncology Center: Washmgton Unrw SchwlofMedicine. 4939 Children kPlacc/Suile SJOO, SC Louis, MO 63110 Lung Cancer (Ireland) 1994;l I:Suppl 3:Sll7-8.

Lung cancer continues to be a major health problem worldwide. In spite of significant technological and scientific medical progress, the final outcome of