228 Abstracts/Lung Cancer I3 (1995) 185-232

infiltrating lymphocytes, ranging from 4 to 70 billion cells, were reinfused intravenously 4 to weeks after operation. Interleukin-2 was administered subcutaneously at escalating doses for 2 weeks and then at reduced doses for 2 to 3 months. Median survival was 14 months. and the 2- year survival was 40%. Three patients remain alive and disease-free at more than 2 years after operation. Two of these patients did not have complete resection at thoracotomy. Multivariate analysis showed no correlation between the factor of incomplete resection and survival. Intrathoracic recurrence without concomitant distant failure was documented in two patients only and none of the patients with incomplete resection (12 cases) had relapse within the thorax. The present experience demonstrates that adoptive immunotherapy may be applied with safety in patients operated on for stage III non-small- cell lung cancer and suggests that it can be useful, notably in patients with locally advanced disease.

Radiotherapy plus carboplatin and teniposide in patients with brain metastases from non small cell lung cancer Pronzato P, Bruna F, Neri E, Roveri D, Trabucchi A, Vanoli M et al. Isr. Nazionole Ricerco sul Cancro, Lisle Benedetto,XT IO, 16132 Geneva. Anticancer Res 1995;15:517-9.

Background. The role of chemotherapy alone or added lo radiation treatment for the palliation of multiple, unresectable brain metastases from non small cell lung cancer (NSCLC), is not yet well defined. Carboplatin and teniposide, however, are an interesting combination in this setting since they are active in NSCLC and because of encouraging results against brain metastases in other tumor types. Methods. Twenty patients with brain metastases from NSCLC were treated with whole brain irradiation (total dose of 45 Gy) and chemotherapy (carboplatin, 300 mg/sm on day 1 and teniposide, 60 m&m on days 1, 2 and 3). Results. Nine patients (45%) showed a complete remission of neurologic symptoms, and 7 (35%) an improvement. Neurologic signs disappeared in 8 patients (40%) and improved in 7 (35%). Three patients (15%) had partial (50%) regression of brain metastases at CT scan, and also showed response in other tumor sites. One other patient had a response ofchest and liver lesions, while the cerebral metastases remained stable. Median survival was 7 months with a range of I-9 months. Toxicity was mild, with no toxic deaths. Conclusions. Aggressive treatment can be taken into consideration also in the case of NSCLC patients with brain metastases and negative prognostic features. Their participation in clinical trials should be encouraged, since this will allow definition of the contribution of combined radiotherapy, chemotherapy and supportive care to the quality and duration of the patient’s life.

Neoadjuvant chemotherapy of locally advanced non-small cell lung cancer Pujol J-L, Le Chevalier T, Ray P, Gautier V, Rouanet R Arriagada R et al. Hopital de Arnaud Villeneuve, Centre Hosp. Regional/ Universifaire. 34295 Montpellier Cedex 5. Lung Cancer (Ireland) 1995;12:Suppl l:S107-18.

Neoadjuvant chemotherapy was tested in non-small cell lung cancer in an attempt to increase the resectability of the tumor and to treat the microscopic metastatic disease known to be responsible for the majority offailures in surgically treated patients. This review deals with published trials. Most of them are feasibility studies in Stage III NSCLC. Obviously, the heterogeneity ofeligibility criteria &om one study to another prevents general conclusions on the usefulness of neoadjuvant chemotherapy. However, it is possible to conclude that neoadjuvant chemotherapy has an antitumor activity: the majority of the studies report a 60% objective response rate including a significant number of complete responses and a 50% complete resection rate. Neoadjuvant chemotherapy does not

increase morbidity after surgery except when it is combined with preoperative radiation therapy. At the time of writing, one Phase III randomized study comparing neoadjuvant chemotherapy followed by surgery with surgery alone has been published. This study concludes that the combined modality treatment improves the survival of patients with locally advanced non-small cell lung cancer. Taken as a whole, the literature deserves further studies to determine the place of neoadjuvant chemotherapy in lung cancer.

Multimodality therapy in unresected stage III non-small cell lung cancer: The American Cooperative Groups’ experience Green MR. Cancer Center Clinic, Universi& oJCalifornia, 200 West Arbor Drive, San Diego, CA 92103-8421. Lung Cancer (Ireland) 1995;12:Suppl l:S87-S94.

Since the mid-1980s. the American Cooperative Cancer Treatment Groups (Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, North Central Cancer Treatment Group, Radiation Therapy Oncology Group, Southwest Oncology Group) have performed several multimodality trials exploring combinations of chemotherapy and radiation in patients with Stage III non-small cell lung cancer. The initial trials had a sequential design with induction chemotherapy followed by radiation. Later trials have emphasized concurrent chemoradiation with or without induction chemotherapy. These trials have begun to have an impact on what is considered ‘standard’ therapy for patients with Stage III non-small cell lung cancer (NSCLC).

A phase II trial of combined chemotherapy and surgery in stage IIIA non-small cell lung cancer Darwish S, Minotti V, Crino L, Rossetti R, Fiaschini P, Maranzano E et al, Department ofMedical Oncology, Policlinico, 06122 Perugia. Lung Cancer (Ireland) 1995;12:Suppl l:Sll-S78.

A poor prognosis for patients with Stage IIIA clinical N2 treated by surgery alone has led clinical researchers to find a new treatment modality to improve the curative potential of surgery. Many Phase II trials have been carried out with induction chemo- or chemo- radiotherapy prior to surgery. From June 1988 lo July 1991.46 patients with non-small cell lung cancer (NSCLC) Stage IIIA clinical N2 entered a Phase II induction-chemotherapy trial. Patients received 2-3 cycles of high-dose cisplatin and etoposide. Forty-five were evaluable for response; the response rate was 82% (37/45: 3 CR, 34 PR). Toxicity was primarily hematologic. Surgical resection was performed in 35 patients; radical resection was possible in 28 patients (62%); three patients were incompletely resected and two patients were only explored. Three deaths were surgery-related. Median survival was 24.5 months with a 2-year survival of 53%. Cisplatin with etoposide is an active and safe induction chemotherapy regimen for NSCLC Stage IIIA N2 with a high response rate. The median survival seems to be prolonged and therefore. randomized trials are needed to compare this approach with other treatment modalities.

Effectiveness and toxicity of preoperative therapy in Stage IIIA non-small cell lung cancer including the Memorial Sloan- Kettering experience with induction MVP in patients with bulky mediastinal lymph node metastases (Clinical N2) Kris MG, Pisters KMW. Ginsberg Rl, Rigas JR Miller VA. Grant SC et al. Memorial Sloan-Kettering Cancer Ct,: 1275 York Avenue, New York, NY 10021. Lung Cancer (Ireland) 1995;12:Suppl l:S47-S57.

The use of preoperative chemotherapy with mitomycin, vinblastine and cisplatin (Mvp) has led to improved complete resection rates and survival in Stage IIIA non-small cell lung cancer with bulky, ipsilateral.

Abstracts/Lung Cancer 13 (1995) 185-232 229

mediastinal lymph node metastascs (Clinical N2 disease). The addition of preoperative irradiation has also been explored with results not substantially different from preoperative cisplatin-based chemotherapy alone. While preoperative chemotherapy has been shown to be feasible, the toxicity of both the chemotherapy and the subsequent resection is of concern with an overall treatment-related mortality of nearly 8%. The careful selection of patients, swig management of neutropenia, and meticulous perioperative pulmonary care has the potential to reduce the mortality from multimodality therapy. Having shown survival benefit in multiple single-institution and randomized trials, induction chemotherapy followed by surgery or irradiation is now the treatment of choice for patients with Stage IIIA non-small ceil lung cancer with mediastinal lymph node metastases.

Perioperative chemotherapy and surgery for unresectnble non- small cell lung cancer - A report of two cases Takigawa N, Makihara S, Numata T. Department o/lnternalMedicine, National Sanatorium Sanyousou Hosp.. Yamaguchi. Jpn J Chest Dis 1995;54:333-8.

Two patients with ummectable non-small cell lung cancer underwent perioperative chemotherapy and surgery. Patients received ifosfamide I .3 g/m* on day 1 to 5; cisplatin 20 mg/m’ on day I to 5; and vindesine 3 mg/m’ on day 1 and 8; with lenograstim 75 ig/m* on day 9 to 22. The courses were repeated every 4 weeks. A clinical tumor response was evaluated after each coorse of chemotherapy. At the time when the tumor was considered to be resectable, surgery was undertaken. AS the perioperative chemotherapy, four courses were repeated before and after the surgery. As the result one patient was proved pathologicaRy tobecome free from tumor. This perioperative chemotherapy and surgery is well- tolerated and effective as one of multimodality managements for regionally advanced non-small cell lung cancer.

Concurrent hyperfractionated irradiation and chemotherapy for unresectable nonsmall cell lung cancer: Results of radiation therapy oncology group 90-15 Bybardt RW, Scott CB, Ettinger DS, Curran WJ, Doggett RLS, Coughbn C et al. Department of Radiation Oncology, Medical College of Wisconsin, 8700 West Wisconsin Avenue, Milwaukee, WI 53226. Cancer 1995;75:2331-44.

Backgrtxmd. Clinical trials of hyperfractionated radiation therapy and induction chemotherapy followed by standard radiation therapy have shown improved survival in patients with unresectable nonsmall cell lung cancer (NSCLC). Radiosensitization may improve local tumor control when chemotherapy is given concurrently with hyperfractionated radiation therapy, but also may increase toxicity. A Phase I/II trial, Radiation Therapy Oncology Group YO- 15, was designed to evaluate whether this strategy could improve survival with acceptable toxicity and be part of a Phase III trial of chemoradiation sequencing. Methods. Vinblastine (5 mg/IvP weekly x 5 weeks) and cisplatin (75 rnfl days 1, 29, and 50) were given during twice-daily irradiation (1.2 Gy, 6 hours apart) to 69.6 Gy in 58 fractions in 6 weeks. Eligible patients had American Joint Committee on Cancer (AJCC) Stage II (umesected) or IIIA- B NSCLC and Karnofsky performance status 70 or greater; there were no weight loss restrictions. Resuifs. Of42 eligible patients, 76% had greater than 5% weight loss, 45% had T4 primary tumors, and 62% were Stage 115. All pmtocol treatment was completed in 53%. Acute toxicity was predorninantIy hematologic with 19 of 42 (45%) having Grade 4 toxicity or higher, three (7%) with septic death. Ten of 42 (24%) had Grade 3 or higher esophagitis. There were two (4.7%) patients with Grade 3 or higher (1 lung and 1 esophagus) and two (4.7%) with Grade 4 or higher (1 lung and 1 hematologic) late toxicities. Median survival time was 12.2 months, with an overall l-year survival

of 54%, an estimated 2 year survival of 28% and a l-year progression free survival of 38%. Conclusions. For patients with unresectable non- small cell lung cancer, who were. not selected on the basis of weight loss, concurrent hyperfractionated irradiation and chemotherapy had more intense acute toxicity than hyperfractionation alone, but late toxicity was acceptable. One and 2-year survival rates were 54 and 28%, respectively.

Concurrent chemoradiotherapy followed by surgery for advanced stage III non-small cell lung cancer (NSCLC) Katakami N. Matsumoto H. Tomioka H. Okazaki M. Hasegawa T. Sakamoto H. Pulmonary Unit, Kobe Cify Generai Hospital, Kobe. Jpn J Cancer Chemother 1995;22:531-7.

Forty-two patients with stage IIIA (bmnchoscopically T, and/or bulky N,) and stage IIIB NSCLC were treated with concurrent chemo- radiotherapy (CRT). Treatment consisted of CDDP, 20 mg/m* and etoposide, 40 mg/m* by continuous iniitsion (day l-5) of weeks 1 and 5 simuhaneousIy with chest radiotherapy (RT), 50 Gy, 2 Gy/Fx, 5 Fx/ week. Surgery was attempted 3-5 weeks after RT in pts clinically downstaged. Between lO/YO and 12/92,43 previously untreated pts were enrolled and 42 were eligible. Pts characteristics were: male/female = 3715; mean age, 61 yrs (range, 31-74 yrs); stage IIIA/IIIB = 10132; 15 adenocarcinoma, 24 squamous cell, 2 large cell, 1 unclassitied; PS O/l/ 2 = 11/24/7. Excluding 1 ineligible pts, 42 pts were evaluated for CRT response. The response rate was 81% (1 CR 33 PR, 5 NC, 1 PD, 2 NE). Clinical downstaging was achieved in 20 pts (48%). Twenty-one pts (50%) received surgery and 19 of them were completely resected. In 7 resection specimens, no tumor was observed. Toxicity of CRT was well tolerable (Grade 4 leukopenia. 15%; Grade 2-3 esophagi& 15%). We conclude that this intensive combined modality therapy is acceptable and appears to increase the response rate as well as resectability. Prospective. randomized studies should be conducted for further evaluation of this treatment modality.

Phase II study of concurrent radiotherapy and chemotherapy for unresectable stage III non-small-cell lung cancer Funtse K, Kubota K, Kawahara M, Kodama N, Ogawara M, Akira M et al. Department ofInternal Medicine, Natl. Kinki Centr Hosp. Chest Dis., 1180, Nagasone-cho, Sakai, Osaka591. J Chn Oncol1995;13:869- 75.

Purpose: To evaluate the response rate. toxicity, and 2-year survival rate of concurrent radiotherapy and chemotherapy for unresectable stage III non- small-cell Lung cancer (NSCLC). Patients and Methods: Between July 1989 and October 1990, 65 patients with histologically or cytologically proven unresectable stage III NSCLC without T3NO- 1MO disease were entered onto this study. Sixty-one patients were eligible for response, survival, and toxicity analysis. Chemotherapy consisted of vindesine (3 mp/m’ on days 1, 8, 29, and 36), cisplatin (100 mg/m* on days 1 and 29), and mitomycin (8 mg/mr on days 1 and 29). Radiotherapy was administered for 3 weeks (2 Gy given 13 times, five fractions per week), folIowed by lo-day rest periods and then the previous schedule of radiotherapy repeated for 3 weeks. Results: Of 6 1 eligible patients, 53 (S6.Y%) had a partial response (PR). The median response duration was 39.1 weeks (range, 8.4 to 163+). The median survival time was 16 months and the 2-year survival rate was 36.7%. Of 53 responding patients, 10 (16.4%) arc alive and disease-free after 2 years. The major toxicity was leukopenia ( grade 3.95%). Other toxicities of grade 3 included thrombocytopenia (45%) anemia (28%). nausea/