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glycoprotein mRNA. In three independent selections for doxorubicin resistance, MDR variants arose in which mdrl P-glycoprotein mRNA and protein was not detectable. Selection on higher doxorubicin con- cenuations gave rise to variants containing high levels of mdrl mRNA, due to transcriplional activation of the mdrl gene. Upon continued selection for higher levels of doxorubicin resistance, the mdrl gene became amplified, resulting in an additional increase in the level of mdrl mRNA. The cross-resistance pattern of the sublines that lack mdrl P-glycoprotein expression is different from chat seen in the mdrl overexpressing cells. Both types of MDR cell lines are resistant to doxorubicin, daunorubicin, etoposide, colchicine, gramicidin D, and vincristine. However, in the non-P-glycoprotcin-mediated MDR cell lines, resistance levels are lower and a preferential resistance for etoposide is seen.

Small cell bronchogenic carcinoma: A cyclical alternating combi- nation of epirobicin plus cisplatin and cyclophosphamide plus etoposide Casadio M, Lelli G, Giordani S et al. Oncology Deparfmenr SC. Orsola- Ma@ghi Hospiral. via Albermni 15. J Chemother 1990;2:199-202.

Forty-seven patients with advanced small-cell bronchogenic carci- noma (SCLC) were treated with a combination of epirubicin (4.EPIDX) (60 mg/m’ i.v.) and cisplatin (CDDP) (50 mg/m2 i.v.) on day 1, alternated with cyclophosphamide (CTX) (800 mg/m’ i.v.) day 1 and etoposide (VP16) (120 mg/m’ i.v.) on days 21-23. Four patients (9%) obtained a complete remission and 27 (57%) a partial remission with an overall remission rate of 66%. The median duration of response was 37 weeks (range 13- 150) and the median duration of survival was 43 weeks (range 10-150). No severe bone marrow depression was noted. The other side-effects were of a mild grade.

L-2,4 diaminobutyric acid as a new therapeutic principle in the management of human bronchial neoplasms HedinG,RonquistG,NouE,Bergh J.lnstiluteofC[inicalBacleriology. Uppsala University, Box 552, S-75122 Uppsala. Int J Exp Clin Che- mother 1990;3:23-30.

L-2.4 diaminobutyric acid (DAB) induced complete cellular lysis when in vitro added to a growth medium for different cell lines derived from lung cancer. The concentration of DAB required for 100% lysis varied from 22.5 mmol/l for cell line U-1690 (most sensitive) to 37.5 mmol/l for cell lines U-1752 and U-1906. Another cell line (U-1810) was intermediate in regard to DAB sensitivity. DAB administered twice daily for 12 days to 5 patients with non-small-cell lung cancer, stage IV, did not lead to any objective improvement, but 4 of the 5 patients showed markedly necrotic tumors at autopsy. DAB treatment resulted in toxicsideeffects,amongwhich neurologicalonespredominated.The possible mechanisms and the management of the side effects are discussed.

Potentiation of cisplatin by alpha-Interferon in advanced in non- small cell lung cancer (NSCLC): A phase II study Bowman A, Fergusson RJ, Allan GS, Stewart ME et al. University Deparrment of Clinical Oncology, Western General Hospital, Edin- burgh EH4 2XU. Ann Oncol 1990;1:351-3.

Studies in experimental human lung cancer models have suggested that interferon may enhance significantly the response to some cyto- toxic drags. We have performed a phase II study of cispladn (100 mg/ m2 q.21 or 28 days) and alpha-2 interferon (3 or 5 MU three times weekly) in 68 patients with advanced non-small cell lung cancer and good performance status. As toxicity was acceptable, the dose of interferon and schedule of cisplatin were increased at the midpoint of the study. 46% (1 l/24) of patients with squamous carcmoma responded and an overaIl partial response rate of 30% was attained in 60 evaluable patients. There was no potentiation of haematological, renal or neuro- logical toxicity but nausea and vomiting were severe. These results suggest that the combination has activity in this usually refractory disease.

Radiotherapy

Radiation therapy for medically inoperable stage I and II non-small cell long cancer Armstrong JG, Minksy BD. Deparmwu ofRadi&ion Oncology. Memorial Sloan-Kettering Cancer Cenrer, 1275 York Avenue, New York, NY 10021. Cancer Treat Rev 1989;16:247-55.

The published results of primary radiation therapy for early slage NSCLC, indicate that it is a reasonable alternative in patients with medical contraindications or who refuse surgery, resulting in accept- able morbidity, local control, and survival rates. There is no conclusive evidence that EMI is of benefit. Consequently treatment with involved field alone, may be considered when there is no evidence of hilar involvement, or when its is necessary LO limit the volume of lung tissue irradiated. Although the data are not conclusive, there is evidence to suggest that the total dose of radiation delivered to the primary should be sufficient to eradicate gross disease (60 Gy or higher). Such doses result in high reponsc rates particularly for Tl tumors. There is also an indication that complete responders have beiter survival than other patients, suggesting that radiotherapeutic strategies to enhance tumor eradication may improve survival.

Endobronchial radiation therapy (EBRT) in the management of lung cancer Roach M III, Leidholdl EM Jr, Tatera BS, Joseph J. Radiarion-Oncol- ogy Service, VA Medical Center, 150 Muir Road, Martinez, CA 94553. Int J Radiat Oncol Biol Phys 1990;18:1449-54.

Between October 1987 and November 1988, 19 endobronchial Iridium- 192 line source placements were attempted in I7 patients with advanced incurable lung cancer. Approximately 30 Gy was delivered to the endobronchus using a low dose rate (LDR) afterloading technique delivering a mean dose of 709 cGy/hr at 5 mm. Improvement in subjective symptoms was noted in 67% of evaluable patients whereas objective responses defined by chest X ray and bronchoscopy were noted in 26% and 60%, respectively. No significant morbidity was observed. The radiation exposure to health care workers was low ranging from 10 to 40 mRem per treatment course wilh most of the staff receiving less than 10 mRem per treatment course (minima1 detectable level 10 mRem). The results of this series are compared with selected series using low dose rate as well as intermediate dose rate (IDR) and high dose ralc (HDR) cndobronchial radiation therapy (EBRT). Based on bronchoscopic responses from the selected series reviewed, both HDRlowto~ldoseper~ca~cnt(range7.5-10Gy)andLDRhightotal dose per ueatmem (range 30-50 Gy) are effective in palliating the vast majority of patients with endobronchial lesions. Intermediate dose rate is also effective using fractions similar to high dose rate but total dose similar to low dose rate. The efficacy of endobronchial radiation therapy in Ihe palliative setting suggest a possible role for endobron- chial radiation therapy combined with external beam irradiation with or without chemotherapy in the initial management of localized lung cancer. Delining the optimal total dose, dose rate, and the exacl role of endobronchial radiation therapy in the management of lung cancer will require large cooperative trials with standardization of techniques and definitions.

Intermediate dose rate remote afterloading brachytherapy for intraluminal control of bronchogenic carcinoma SpiserB, SpratlingL.DeparmzentofRadiulion Oncology,St. Joseph’s Hospital andMedical Center.350 W. ThomasRd.. Phoenix.AZ8S013. Int J Radiat Oncol Biol Phys 1990;18:1443-8.

Forty-five patients with symptomatic proximal malignant airway disease received 128 intraluminal intermediate dose rate (IDR) bra- chytberapy treatments by remote afterloading technique. Multiple small catheters were bronchoscopically placed. Iridium-192 sources delivering an intermediate dose rate (200- loo0 rads/br) were guided under remote computer control. Treatment times were l-4 hr. Fourteen of these patients also received YAG laser photoresection. External