348 Abstracts/Lung Cancer 13 (1995) 323-356

mOduhtOf Of P-glyqXOtein tiutction, was able to reverse drug resistance and to increase drug accumulation. In Northern-blot analysis no differences in expression of topoisomerase I and II (a and 6). DNA polymemse 6, or HSP70 and HSP60 genes were observed between PQClB and PQGB/DX. Coupled to lack of changes in expression of known resistance &tots, overexpression of MRP and modulation by verapantil strongly support a role for this gene product in the development of drug resistance in this SCLC cell system. This study provides evidence that (a) altered cellular pharmacokinetics is related to MRP expression: @) MRP-mediated phenotype is characterized by a specific pattern of cross- resistance, which does not involve taxol; and (c) verapamil may be effective in modulating the function of the MRP gene product.

High dose intensification chemotherapy with autologous bone marrow transplantation in small cell lung cancer. A pilot study Luo KH, Shi YK, Sun Y, Wang QL, Feng FY, Feng QF et al. Depurtment of Internai Medicine, Sichuan Cancer HospitaI, Chengdu 61554i. Sichuon Pmvince. J Exp Clin Cancer Res 1995;14:197-203.

File out of nine patients with small cell lung cancer (SCLC) intended for high dose chemotherapy and autologous bone marrow transplantation (ABMT) completed ABMT while the other 4 were excluded due to contraindications. Primary tumors hadbeen resected before the inclusion in two of them. Four cycles of chemotherapy had been conducted before ABMT, and partial remission (PR) had been obtained in the other three. The preparative regimen consisted of catboplatin 500-600 mg/ml, epirubicin 60-75 mg/m* and etoposide 450-1200 mglm’. PR was converted to complete remission (CR) in one patient while the others remained stable after ABMT. Severe non-hematologic toxicities were observed during this period. All 3 non-operated patients subsequently received chest irradiation (60 Gy) f prophylactic bilateral supmclavicular irradiation (40 Gy). only one patient was in event-free survival by the time of final follow-up. The reasonable procedure for such a setting should be further investigated.

Radiotberapy alone for non-amall cell lung carcinoma. Five-year disease-frze survival aad patterns of failure Koukourakis M, Skarlatos J, Kosma L, Geatromanolaki A, Yammkakis AD. 18 Dimokratias Avenue. Iraklion 71356, Crete. Acta Oncol 1995;34:525-30.

One hundred and fifty-three patients with inoperable non-small cell lung cancer (NSCLC) treated with radiotherapy alone have been retrospectively analysed. Normalized Total Dose (NTD) as defined by Macejewski, TN-stage (AJC-system) and histology have been examined with respect to 5-year disease-free survival (DFS) and the patterns of failure so as to identify subgroups of patients that routinely should be treated with radical intent. The S-year DFS for Tl, 2-NO, 1 and T3-NO, 1 staged patients was 30% (7123) and 25% (4/16) respectively when the tumor NTD (a/b = 10 Gy) was 5664 Gy vs. 12% (5/41) and 0% (O/IO) when the NTD was 48-55 Gy. This di&.rence was statistically signiticant for the squamous cell histology group. The higher doses signifmantly altered the patterns of death in NO, I staged squamous cell carcinoma and adenocarcinoma patients. Forty-five percent (22/55) and 41% (12/ 29) of squamous cdl and adenocarcinoma patients mspectively, died from local relapse without evidence of distant metastases when NTD less than 55 Gy were given vs. 21% (9142) and 13% (2115) when the NTD delivered was 5664 Gy @ < 0.05). Although for N2, 3 staged patients or patients with direct extension of the tumor into the medlastinum death from local relapse occurmd in 38% (10126) of the highNTDtreatedpatientsvs.51%(19/37)ofthelowdosetreatedones, the difference was not statistically significant. It is concluded that NSCLC patients should not a priori be considemd as non-radiocurable. At least 30% of the patients with early local stages can be long-term

disase-free survivors with radiation NTD up to 60 Gy andbetter results are to be expected with higher doses. Advanced T-stage without mediastinal involvement should be treated with radical intent since a high NTD could give cure rates of over 25%. The disappointing results for patients with mediastinal disease could perhaps be attributed to the low NTD delivered. For patients with good performance status, hyperhactionated regimens delivering high tumor doses should be tested and chemotherapy should be adapted to these radiation treatment schedules.

Integration of vhuuelbine into cbemotberapy strategies for non- small-cell lung cancer Vokes EE. Dept. ojMedicine/Rodiation Oncology, Clniversiw oj Chicago, Cancer Reseord Center 5851 SEllisAve.. Chicago, IL 65637. Oncology (USA) 1995;9:565-574+577.

Meta-analyse~ of randomized clinical studies comparing combination chemotherapy versus ‘best supportive care’ for advancd non-small- cell lung cancer have revealed a small, but statistically s&nificant survival advantage for patients who receive chemotherapy. However, overall increases in l&span have been short, and the great majority of patients die within I year of diagnosis. In the last few years, several new drugs with promising activity have been identified. Of these, vinorelbine has already been shown to increase survival rates in randomized clinical trials. In particular, one such trial showed the combination ofvinorelbhte and cisplatin to result in statistically superior survival rates, compared with ‘standard’ therapy of cisplatin and vindeaine, and with single-agent vinorelbine. A second study comparing vinorelbine to fluorouracibleucovorin also demonstrated a smvival benefit for patients treated with vinorelbine. Therefore, the combination ofvinorelbine and cisplatin represents one new option for initial therapy of newly diagnosed stage IV non-small-cell lung cancer.

Pilot study of irinotecan in refractory small cell lung cancer Fujita A, Takabatake H, Tagaki S, Sekine K. Jpn J Cancer Chemotber 1995;22:889-93.

Sixteen patients with refractory small cell lung cancer (SCLC) were treated with an itinotecan starting dose of lOOmg/m~ given as a 90- minute iv iniitsion every week with subsequent doses based on toxicity. Mean age was 64 years; 14 male and 2 female; 4 with limited disease and 12 with extensive disease; all patients pretreated with combination chemotherapy containing etoposido. The overall msponse rate was 500/o (95%CI25-75%)withnoCRand8PRThen~diandurationofresponse was 46 days. Major toxicities were leukopenia, diarrhea and pulmonary toxicity. Irinotecan was thus an effective agent in refractory SCLC.

A phase II study of paclitasel and granulocyte colony- stimulating factor in previously untreated patients with extensive-stage small cell lung cancer: A study of the North Central Cancer Treatment Group Jett JR, Klrschling RJ, Jung S-H, Marks RS. Pittsburgh Cancerhrstitute. KauJFnan Bldg# 3471 Fif?h Ave, Pittsbwgh. PA 15213. Semin Oncol 1995;22:Suppl 6:75-7:

In 1994, approximately 34,000 to 43,000 Americans will be diagnosed with small cell lung cancer, and 60% to 70% of these individuals will have extensive-stage disease. The median survival time of patients with extensive- stage small cell lung cancer is 8 to 10 months and 10% or less will survive 2 years. There have been no major advances in the treatment of this stage of disease in the past decade. Phase II trials with promising new single-agent chemotherapeutic drugs are justifiable. We report the design and toxicity of a phase II trial with single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in previously untreated patients with extensive-stage small cell lung cancer.