274

Mucositis (grade II in six patients, grade

III-IV in seven patients) was the dose-li- miting toxicity, especially in Group 2. These responses to cisplatin bolus and 5-FU infusion in patients with non-small cell lung cancer were not greater than those achieved with other cisplatin-containing regimens. However, this combination does have activity and might be effectively com- bined with radiation therapy as has been done for carcinomas of other sites.

Phase II Study of Vindesine in Patients with Non-Small Cell Lung Cancer. Fujita, J., Saijo, N., Eguchi, K. et al. Department of Internal Medicine, National Cancer Center, Chuo-ku, Tokyo 104, Japan. Jpn. J. Cancer Res., Gann 76: 902-905, 1985.

A phase II of vindesine (VDS) was car- ried out in 21 patients with non-small cell lung cancer (NSCLC). There were 13 and 8 patients with and without prior chemotherapy, respectively. VDS wa~ administered at a week- ly iv dose of 3 mg/m-. Partial response was observed in two of 15 adenocarcinomas and one of 2 adenosquamous cell carcinomas, and the overall response rate was 14.3% (3/21). Myelosuppression, especially leuko- penia, was the most common dose-limiting side effect. Neurotoxicity was also a common side effect but the degree was mild. I~ was concluded that VDS at a dose of 3 mg/m- every week seems to be active against NSCLC.

Phase II Study of the Three-Drug Combination of Mitomycin C, CCNU, and Methotrexate (MC~ in Advanced Non-Small Cell Lung Cancer. Eagan, R.T., Frytak, S., Richardson, R.L. et al. Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, U.S.A. Am. J. Clin. Oncol., Cancer Clin. Trials 9: 67-70, 1986.

Ninety-two patients with advanced non- small cell lung cancer, 51 without prior chemotherapy exposure, were treated with the combination of mitomycin C, lomustine (CCNU), and methotrexate (MCM). Overall, the regression rate was 33%, the median regres- sion duration 4.9 months, and the median survival 4.9 months. Patients with ECOG performance shores (PSs) of 0-i had a sta- tistically significant higher regression rate than did patients with ECOG PSs of 2-3 (43% versus 15%; p = 0.005) as did patients without prior chemotherapy (41% versus 22%; p = 0.005). Cell type and prior chemothera- py exposure did not affect regression dura- tion, time to progression, nor survival. Sub- jective toxicity was quite acceptable. Cu- mulative myelosuppression was the most signi- ficant objective toxicity. MCM is a relati- vely effective combination chemotherapy re- gimen, even in patients with prior chemo- therapy exposure (predominantly doxorubicin

and cisplatin-based chemotherapy).

Vinblastine Plus Cisplatin in Advanced Non- Small Cell Lung Cancer: Lack of Advantage for Vinblastine Infusion Schedule. Huberman, M., Lokich, J., Greene, R. et al. Section of Medical Oncology, New England Deaconess Hospital, Boston, MA 02215, U.S.A. Cancer Treat. Rep. 70: 287-289, 1986.

We have evaluated 31 patients with ad- vanced non-small cell lung cancer treated by short-term 5-day vinblastine infusion combined with bolus cisplatin. Nine of 31 patients (29%) had partial and complete re- sponses. Although five of nine (55%) of the responders were alive at > or = 1 year, three of the 31 patients experienced drug-related mortality. Out experience, as well as a re- view of previously reported trials in the literature, suggests that the infusion sche- dule of vinblastine offers no advantage over the bolus schedule.

A Randomized T r i a l of the Four Most Act ive Regimens fo r M e t a s t a t i c Non-Small-Cell Lung Cancer. Ruckdeschel, J.C., Finkelstein, D.M., Ettin- ger, D.S. et al. Albany Medical College, Division of Oncology, Albany, NY 12208, U.S.A.J. Clin. Oncol. 4: 14-22, 1986.

Between October 1981 and June 1983, the Eastern Cooperative Oncology Group (ECOG) conducted a prospectively randomized trial (EST 1581) of the four most active chemo- therpay regimens for metastatic non-small- cell lung cancer (NSCLC). Four hundred eighty-~ix good performance status patients (PS 0 or i; 81%) were randomized to receive cyclophosphamide, doxorubicin, methotrexate, and procarbazine (CAMP); mitomycin, vinbla- stine, and cisplatin (MVP); etoposide and cisplatin (VP-P); or vindesine and cispla- tin (VDA-P). All regimens were administered in the doses and schedules originally repor- ted. Complete response (CR) plus partial response (PR) rates for the four regimens were CAMP, 17%; MVP, 31%; VP-P, 20%; and VDA-P, 25%. The response rate for MVP was significantly higher in patients with squa- mous and adenocarcinoma histologies, but there was not impact on median survival (overall, 24.5 weeks). The duration of re- sponse did not differ by treatment as previ- ously suggested for VDA-P. There were 15 CRs (CAMP, one; MVP, six; VP-P, two; VDA-P, six), and 12 patients have survived more than 2 years. Toxicity Was significant with 20 treatment-related deaths. CAMP was signi- ficantly less toxic than the other regimens (P < .001). VDA-P demonstrated significantly more life-threatening (seven) and lethal (three) episodes of nephrotoxicity (P < .001)

-~espite an aggressive hydration program that in itself caused significant morbidity. Ana- lysis of the toxicity data showed, however, that most of the severe toxicity occurred in

the 19% of patients who were initially PS2,

275

s~gesting that they are not appropriate ca~didates for trials of new agents or com- binations. None of these regimens can be recommended as a standard therapy for meta- static NSCLC.

Phase II Evaluation of a Combination of Mi- tomycin C, Vincristine, and Cisplatin in Advanced Non-Small Cell Lung Cancer. Chang, A.Y.-C., Kuebler, J.P., Tormey, D.C. et al. St. Mary's Hospital, University of Rochester School of Medicine and Dentistry, Rochester, NY 14611, U.S.A. Cancer 57: 54-59, 1986.

The combination treatment of mitomycin C (M), vincristine (V), and cisplatin (P) (MVP) in 63 patients with advanced non- small cell lung cancer (NSCLC) were evalu- ated for their potential synergistic cyto- toxicity. The overall response rate was 43% (27/63); in the 54 eligible and evalu- able patients, the response rate was 50% (27/54). Responses were observed in all cell types and disease sites. Cell type; perfor- mance status of 0, i, or 2; sex; and age younger or older than 60 years did not Zig- nificantly influence the response rate. However, patients'with prior radiation had significantly more treatment failure than those without. The dose-limiting side ef- fects in these 54 patients were myelosup- pression (40%), pulmonary fibrosis (9%), pe- ripheral neuropathy (6%), and intractable nausea and vomiting (4%). The degree of leu- kopenia (P < 0.01) but not of thrombocyto- penia increased significantly in patients who had received prior radiotherapy. One patient died of marked thrombocytopenia and one of fulminant hepatitis. Patients who responded lived significantly longer than those who did not (P < 0.004). A majo- rity of the responders (82%) also achieved symptomatic palliation. With appropriate dose modification and supportive care, MVP was tolerable. Further trials with this regimen or a modified version are worth consideration.

Therapy of the Advanced Non-Small Cell Bron- chial Carcinoma with Ifosfamide and Etopo- side. Drings, P., Abel, U., Afheldt, U. et al. Krankenhaus Rohrbach, Klinik ffir Thoraxer- krankungen der LVA-Baden, D-6900 Heidelberg- Rohrbach, Germany. Prax. Klin. Pneumol. 39: 833-834, 1985.

Drug therapy with ifos~amide 2 g/m 2 day 1-5 and etoposide 120 mg/mU day 1-3 achieved one complete and 23 partial remissions in 89 patients with histologically confirmed non-small cell bronchial carcinoma. In 35 patients, the tumour remained stationary under therapy, whereas in 30 patients it was progressive. Median survival time was

242 days for all patients, for the patients

~ith complete and partial remission 369 days, for the patients in stationary condi- tion 260 days and for the patients with tumour progression iii days. The remission rate of 28% indicates that this combination is superior to all other, more toxic drug therapy protocols on account of its overall better tolerance.

Drug Therapy of the Non-Small Cell Bronchial Carcinoma with High Dose VP 16: A Dose- Finding Study of Etoposide in Combination with Cisplatin. Gatzemeier, U., Zschaber, R., Hossfeld, D.K., Radenbach, D. Krankenhaus Grosshansdorf der LVA Freie und Hansestadt Hamburg, D-2070 Grosshansdorf; Germany. Prax. Klin. Pneumol. 39: 835-836, 1985.

In a phase I dose-finding study, the toxicity of increasing doses of VP 16 was tested in combination with a constant dosis of cisplatin. It was the aim of this study to find out the maximal tolerable dosis of VP 16 in order to use it in future in phase II and III studies. Seventeen patients with inoperable, non-small cell bronchial carci- noma were treated ~ccording to protocol. Cisplatin i00 mg/m- was given on day i, VP 16 on the days 3, 4, and 5. The results showed that doses between 800 and 1050 mg/m 2 given orally, cause only low dosage-indepen- dent haematological but more considerably dose-dependent gastrointestinal toxicity. Doses of 500 to 700 mg given intravenously induced considerable haematological side effects and, it the dosis was raised, also considerable non-haematological effects. Oral administration of high doses of VP 16 is limited by the gastrointestinal side effects. The maximal tolerable dosis of VP 16, ~iven peranterally, should be about 500 mg/m per treatment course.

Combination Chemotherapy With Vindesine, Etoposide, and Cisplatin in Non-Small Cell Lung Cancer: A Pilot Study of the Southeastern Cancer Study Group. Hainsworth, J.D., Porter, L.L.-III, Johnson, D.H. et al. Division of Oncology, Vanderbilt University Medical Center, Nashville, TN 37232, U.S.A. Cancer Treat. Rep. 70: 339- 341, 1986.

Ninety-two patients with advanced non- small cell lung cancer were treated with a combination chemotherapy regimen containing cisplatin, vindesine, and etoposide. Eigh- teen patients (20%) achieved major responses to therapy (three complete responders and 15 partial responders). Response rates were similar in each histologic subtype. Initial performance status was an important deter- minant of response; 42% of the patients with a Karnofsky performance status > or = 70% responded versus 5% of those with a

performance status < 50%. The median dura-