114

419 420

MALIGNANTATYPICALCARCINOIDOFTHELUNG: ISCHEMOYYIERAPY TRLCANSWRR?

Haxa~&U., Zimmemtao, P. V., Fiioz-Abedi AJohnston N.G., Allen RKA., Mclndoe N., Tbe Priaee Cbar1e.v Hospital, Briabeoe, 4032.

Recently some long-term smvivors of snail all eareinoma of the long (SCLC) have been reclaseiied as malignant aeemeodouioe carcinomas (sometimes eelled meligwot atypical carcinoid MAC). Chu institution ideotified n patients with MAC over an eight year period. 25 petkate had mugieal feseetion with 3 haviog adjuvant chemotherapy. Cbemotberapy alooe was given to 38 patients. of 32 casea awesable for response lV18 (61%) of limited disease (LD) casea bed a complete respoose (CR). 2/14 (14%) of extensive disease (ED) were CR’s. 29 patients with eofticient follow-up have been included in swivel data. A nnmber of different cbemotbempy regimes have been wed.

‘llte smvivei of the chemotherapy group wee not sigoifieantly different from the magical gmop even tbougb it contained patients with more symptoms, worse performeoce status and more advanced stage. L.D SCLC bed a worse pmgooeie tltatt LD MAC (MST11 vs 35 montbs) although ED SCLC and ED MAC bad similer but much poorer swivel.

‘lltese fiodings suggest that Stage I and ll MAC should be amsidered for mugery. stage lffA and llB disease patients should have ebemotberapy. Stage Iv patients ate as likely as SCLC to have poor survival despite chemotherapy. If patients with MAC were ermnwosly iocluded with LD SCL.C it would explain “long-term survival” in such SCLC series.

421

TWO HIGH-DOSE EPIRUBICIN STUDIES IN UNTREATED POORER PROGNOSIS SMALL CELL LUNG CANCER (SCLC). S.W.Bamham, S.R.Bicknell, G.Allan and R.D.Monie.

Chest Wnits, Royal Infirmary, Stobhill Hospital, Southern General Hospital, Glasgow. A single agent chemotherapy regimen of Epirubicin(Epi) 120mq/m2 iv at 21 day intervals was investigated initially. 26 patients with intermediate (I.P.) or poor prognosis (P.P.) SCLC received a total of 106 cycles of Epi (maximum 6 cycles/patient). Staging consisted of both conventional disease extent and prognostic guidelines based on laboratory parameters. Overall response rate was 57%, but mostly occurred among the I.P. group (14 of 17 patients), compared with only 1 of 9 patients in the P.P. category.

7 patients survived for 12 months (one a 3 year survivor, disease free). Principal toxicity (other than total alopecia seen in all patients) was haemato- logical, but generally easily managed (6 episodes WHO Grade IV neutropenia, 8 patients required blood transfusion). No cardiac toxicity or significant muco- sitis were encountered and chemo response was generally accompanied by improvement in perceived performance rating. A second study combining Epi lCGmq/m2 iv with Etoposide 100mq/m2 iv Day 1 and 100mq/m2 orally Day 2-5 ongoing with 22 patients entered (75 cyclesji Experience thus far suggests an improved tumour response rate but with considerable haematoloqic toxicity (15 episodes WHO Grade IV neutropenia) and mucositis (8 patients WBO Grade II/III). Epi is a highly active agent in SCLC, but its role in future treatment strategies has yet to be fully defined.

Hypatonic cisplatin treatment for carcinomatous pleuritis found at thoracotomy. Y. Ichinose, N. Hara, M. Ohta, H. Asoh, T. Yano.

Dpt. of Chest Surgery, Natl. Kyushu Cancer Ctr., Fukuoka, Japan.

We developed a new intrapleural treatment using combination hypotonic shock and cisplatin (CDDP) for carcinomatous pleuritis found at thoracotomy in patients with non-small cell lung cancer. [Experiment] The growth of three different tumor cell lines was examined in a 3 day culture following 1 min exposure of cells to CDDP in phosphate buffered saline (PBS- CDDP) or water (hypotonic CDDP). CDDP concentration for 50% growth inhibition of these cells in PBS-CDDP and hypotonic CDDP treatment was 14 to 30 pg/ml and 2 to 6 pglml, respectively. Time dependent growth inhibition was observed in hypotonic CDDP (20 pg/ml) treatment and the 3 min treatment resulted in more than 90% growth inhibition of the tumor cells. Small pieces of tumor, which was obtained by resection of lung tumors, were exposed to PBS (control), distilled water, CDDP (50 pg/ml) in PBS or water for 10 min. Viability of tumor was examined by MTT assay in the 6 day culture. When compared to the viability of the control, that in water, PBS-CDDP and hypotonic CDDP treatment was 53, 63 and 26%, respectively. [Clinical results] 11 pts received hypotonic CDDP (50 pg/ml) treatment for 10 - 15 min before closure of thoracotomy. There were no harmful side effects, although the pleura was completely destroyed. Pleural dissemination with or without malignant pleural effusion has been controlled for 6 to 29 months.

422

RANDOMISED CLINICAL STUDY OF VEXAPAMIL IN ADDITION TO CIiF&fO!t.'IiNNAPY IN SMALL CELL LUNG CANCER (SCLC). Milroy R, Paul

J, Cram L, Rafferty P, Hutcheon A, Vernon D, Dorward A, MacIntyre D, Ring D, Stack B, Banham S, Kaye S. Nest of Scotland Lung Cancer Research Group, Glasgow, 631 2ES, UK. The results of the first large-scale rando- mised study of a resistance modifier given with chemotherapy in cancer patients are reported. 226 SCLC pts rece;led 4 cycles of cyclophosp amide (40 mg m- P

(750 mg m )

), doxorubi_cjn and vincristine al.4 mg m )

(d.1) and etoposide (75 mg m- )(d.l to 3), cycle time 21 d. Verapamil (V) patients received oral V 120 mg qid for 5 days with chemotherapy. No significant differences in general (including haematological and cardi- ovascular) toxicities occurred between the 2 arms. Overall response data were similar (p=O.582) although the complete response rate was 39% in the V arm vs. 27% for con- trol. Overall survival was similar in the 2 groups (p=O.29) but median survival of extensive disease patients treated with V was 32 wks. vs. 23 wks. for control (95% CI's 24-48 wks. cf. 10-31 wks.). The absence of a significant improvement in end results using V may relate to low blood levels of V (0.8 micromolar), or to the presence of cellular mechanisms of drug resistance other than P-glycoprotein.