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A PHASE 11 STUDY OF COMBINED CHEMOTHERAPY AND NAO~AT~ON FOR BRAIN METASTASES FROM NON-SMALL CELL CARCINOMA OF THE LUNG G. Ryan, D. Ball, J. Bishop. Peter MacCallum Cancer Instllute, Melbourne, Australia.

Brain metastases develop in -M% of patients with primary carcinoma of the lung. With very few patients suitable for surgery, radiation has been the mainstay of treatment; but despite good symptom palliation, brain metastases remain almost invariably fatal within a short period of time. Chemotherapy has traditionally not been considered appropriate in the primary treatment of brain metastases because of the supposed impenetrability of the brain to cytotoxic drugs. However, in the last five years, a number of studies have documented objective responses to chemotherapy in patients with brain metastases; the blood-brain barrier appears in some way broken down in these patients.

A phase II study of palliative whole brain radiation (20 Gray in 5 fractions over 5 consecutive days) with carboplatin 70 mg/m2 on all days of treatment is being conducted at the Peter MacCallum Cancer Institute. Ninetean patients have been entered on study to this time. There are 0 males and 11 females, with a median age of 61 years (range 36 - 79). Ten patients had brain metastases as their initial presentation with lung cancer; the other Q patients developed brain metastasas at a mean of 8.9 months after diagnosis of non-small cell lung cancer. Ten patients had solitary metastases; multiple leaions were present in 9 patients. Performance status was EC0G 1 in 10 patients, ECXG 2 in 7 patients and ECOG 3 in 2 patients. Treatment has been well tolerated, with 50% of patients being treated as outpatients.

Assessment of radiological response is by followup CT scan six weeks postradiation. Thirteen patients have been assassed radiologically, with 1 complete response, 8 partial responses and 4 patients with stable disease. Median survival from diagnosis has been estimated to ba 5.56 months. The survival of a similar group of 124 patients (EC0G 0 - 2, non-small cell lung cancer) treated at this institution with radiation alone (20 Gray) between 19Q4 and 1987 had an estimated median survival of 4.0 months. The survival of the patients on the pilot study thus represents a 40% improvement in survival over the historical data. A randomized trial is now planned.

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Pilot Studies of the Narth’Centrsl Cancer Treatment Group (NCCTG) CONCURRENT DAILY CARBOPLATIN (CBDCA) AND ACCELERATED Utilizing Accelerated Hyperfrsctionated Thorscic Radiation Therapy HYPERFRACTIONATED THORACIC RADIOTHERAPY (AH-TRT) IN (AHTRT) in Unresectable Stage IIIA/B Non-Small Cell Lung Cancer (NSCLC) LOCALLY ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC). Shaw E, Jett J, Brindle .I, McGinnis W, Maillisrd J, Deming R, K. Watanabe, H. Kunitoh, A. Nagatomo, K. Tanaka and K. Creagan E, Nair 5, Jung S-H, and Knowlton L Kimbara. Dept. of Respiratory Medicine and Radiology, North Central Cancer Treatment Group, Rochester, MN 55905 Yokohama Municipal Citizen's Hospital, Yokohama, Japan.

Materialsfiethods: Between 9/89 and 5/92, 62 patients (pt) were entered an 3 sequsntial NCCTG AHTRT pilot studies, utilizing AHTRT alone (21 pt), AHTRT + Etoposide-Cisplatin (EP) chemotherapy (23 pt), and AHTRT + Interferon-cams (IFN-GM) (18 pt). Patient chsrscteristics were: male-73X, femsle-27%; median age 64 (35-82); ECOG performance status O-1-94%, 2-A%; weight loss <5X-81!& 5-10?&19%; and Stage IIIA-57X, Stage 1116-43X. For all pt, AHTRT consisted of 60 Gy in 40 fractions (fx) of 1.5 Gy RIO, given in 2 equal halves of 30 Gy/ZO fx each, separated by s 2 week break. The Etoposide and Cisplatin doses were 100 mg/m2 and 30 mg/m2 on days l-3 of each half of AHTRT; the IFN-GM dose wss 0.2 mg sub-g on dws O-5 and 7-12 of each half of AHTRT. Rssults: Severe (grade 3), life-threatening (grade 41, or fatal (grade 5) toxicity uss as followa: Grade 3 esophaqitis occurred in 11% of pt.

Concurrent daily cisplatin and TRT prolonged survival compared with TRT alone in patients (pts) with locally advanced NSCLC by improving local control (NEJM 326: 524, 1992). We started a phase II trial of AH-TRT combined with daily CBDCA, chosen because of its longer plasma half life. Pts with MO unresectable NSCLC were treated with twice-daily TRT (1.5 Gy each, 6h apart) to a total of 60 Gy in 40 fractions in 4 weeks. CBDCA as IV bolus of 25 mg/M2 was given immediately before the morning TRT. Twenty-five pts are evaluable. Pts characteristics in- clude: Median age 69 y.o. (range: 46-87), 22 male, perfor- mance status O-l in 16 pts and 2-3 in 9 pts, 3 had clinical stage II diseases, 10 had IIIA, and 12 had IIIB. Two had received prior chemotherapy. L Gr. 3 acute toxi- city by JCOG toxicity criteria (Jpn J Clin Oncol 23: 250, 1993) has included leukocytopenia in 12 (48%), neutropenia in 11 (44%), thrombocytopenia in 4 (16%) and esophagitis in 6 (24%). All pts could complete protocol treatment without delay. There was one fatal pneumonitis 3 months after completion of TRT. AUC of free plasma platinum on day 1 was significantly correlated with surviving fraction of WBC (n=16, r=-0.53, p=O.O4), but not with severity of esophagitis. There were 2 CRs and 20 PRs in the TRT field, for a response rate of 88% (95% C.I.: 69 to 98%). MST was 6.8 months probably because of inclusion of many poor-risk pts, but the survival curve was not mature. This combination treatment seems to have excellent local activity with significant but acceptable toxicity.

_ equally distributed anong the 3 pilot studies. Pnewnitis 1. grade (gr) 3 occurred in 9.5% (2 gr 3) of pt receiving AHTRT alone, 13% (1 gP 3, 2 gr 4) of pt receiving AHTRT + EP, and 44% (6 gr 3, 2 gr 5) of pt receiving AHTRT + IFN-W (p<O.O5). Survival and local-control data is show” below:

Pilot Survival l-year local

Median (na) l-year (a) Z-year (I) control (Z)

AHTRT alone 10.8 48 29 70 AHTRT + EP 26.0 74 52 92 AHTRT + IFN-GH 7.8 38 __ 52

Conclusions: AHTRT alone or + EP has acceptable toxicity with encouraging survivel/lacal control data. AHTRT + IFN-M is excessively toxic (pneumonitis) with disappointing early survival and local control data.

COMBINED SURGERY AND RADIOTHERAPY IN LUNG CANCER D.Y.Xie. Cancer Hospital, Shanghai Medical Univ. Shanghai, 200032, China

There were 1014 cases of lung cancer treated in our hospital frcm 1955 to 1990. Three groups could be classified: Group I, colnbined preopera- tive radiotherapy and surgery in 153 cases. Group II, surgery alone 560 cases, Group IU, co,n- bined sumerv and oostooerative radiotheraov 301 cases. In-gro*p I,- 23 cases belonged to stage II and 130 cases belonaed to staae III. The resection rate were 74.54, their survival rate of 3-year and 5-year were 319 and 20.215 respectively. In group II, stage I: 52 cases, stage It:229 cases and stage IOa: 2RO cases. The resection rate were 59.929, their survival rate of 3-year and 5-year were 52.614 and 39% respectively. In group III, stage II:25 cases and stage IlIa: 275 cases Their survival rate of 3-year and 5-year were 53.824 and 37.71% respectively. In cocnparison to the resection rate of the stage III cases both in group I and in group li,the for,ner was 70% and the latter was 60%. There were 58 cases with hilar lytnph node ‘netastasis or residual tmnor in the grpup JI,who did not accept postoperative radiotherapy, their survival rate of 3-yesr and 5-year were 18.96% and 3.57% respectively. We conclude as follow: 1. preoperative radiotherapy can slightly raise the resection rate in the stage III cases. 2. postoperative radiotherapy offers an opportunity to cure sol&e patients with hilar ly,nph node inetastasis or residual tugnor in which it has been previously considered as incu- rable.

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