Abstracts 1 Lung Cancer 15 (1996) 381-399 391

rate did not significantly differ in the two groups (P = .33). The hvo groups showed similar incidence of acute and late high-grade toxicity (P = .44 and .75, respectively). No treatment-related toxicity was observed. Conclusion: The combination of HPX RT and low-dose daily CBDCA plus VP-16 was tolerable and improved the survival of patients with stage III NSCLC as a result of improved local control.

Concurrent chemoradiation therapy with oral etoposide and cisplatin for locally advanced inoperable non-small-cell lung cancer: Radiation Therapy Oncology Group Protocol 91-06 Lee JS, Scott C, Komaki R, Fossella Fv, Dundas GS, McDonald S et al. Department of Thoracic/HNMo, M.D. Anderson Cancer Cente,: Box 80, ISIS Holcombe Blvd, Houston, TX 77030. J Clin Oncol 1996;14: 105564.

Purpose: Patients with locally advanced inoperable non-small- cell lung cancer (NSCLC) have a poor clinical outcome. We conducted a prospective study to evaluate the merit of chemotherapy administered concurrently with hyperfractionated thoracic radiation therapy. Patients and Methods: Seventy- nine patients with inoperable NSCLC were enrolled onto a multicenter phase II trial of concurrent chemoradiation therapy. Treatment consisted of two cycles of oral etoposide 100 mg/d (50 mg twice daily) on days I to 14 of a ZSday cycle (75 mg/d if body- surface area [BSA] < 1.70 m’), intravenous cisplatin 50 mg/m* on days I and 8, and hyperfractionated radiation therapy 5 days per week (I.2 Gy twice daily > 6 hours apart; total, 69.6 Gy). Results: Seventy-six assessable patients with a Karnofsky performance status 60 and adequate organ function who had received no prior therapy were evaluated for clinical outcome and toxic effects. After a minimum follow- up duration of 2 I months, the 1 - and 2-year survival rates and median survival duration were 67%, 35%. and 18.9 months overall; they were 70%. 42%, and 21.1 months for patients with weight loss of 5 5%. Toxicity was significant; 57% developed grade 4 hematologic toxicity, 53% grade 3 or 4 esophagitis, and 25% grade 3 or 4 lung toxicity. However, only 6.6% of patients had grade 4 or lethal nonhematologic toxicity. which included three treatment-related deaths (two of pneumonitis and one of renal failure). Conclusion: Concurrent chemoradiation therapy with oral etoposide and cisplatin plus hyperfractionated radiation therapy is feasible. The survival outcome from this regimen compares favorably with that of other chemoradiation trials and even of multimodality trials that have included surgery.

Adjuvant chemotherapy atIer complete resection in non-small- cell lung cancer Wada H, Hitomi S. Teramatsu T. Department of Thoracic Surgery, Chest Disease Research Institute, Kyoto University, 53, Kawahara-cho, Shogoin, Sakyoku, Kyoto 606-01. J Clin Oncol 1996;14:1048-54.

Purpose: We performed a study to determine whether postoperative mild chemotherapy to maintain the patient’s quality of life (QOL) and immunoactivily could also prolong survival. Subjects and Methods: From December 1985 to July 1988, 323 patients with completely resected primary non-small-cell lung cancer (stage I to III) were enrolled. The subjects were randomized into three treatment groups, as follows: cisplatin (CDDP) 50 m&m2 body surface, vindesine (VDS) 2 to 3 mg/ kg body weight for three courses, and I-year oral administration of tegafur (FT) plus uracil (UFT) 400 m@g body weight (CWfl group, 115 patients); l-year oral administration of UFf 400 mgtkg body weight (Ufl group, 108 patients); or surgical treatment only (control group, 100 patients). Results: The overall 5-year survival rates were 60.6% for

the CWft group and 64.1% for the UA group versus 49.0% for the control group. The results of statistical testing were P = .053 (log- rank test) and P - ,044 (generalized Wilcoxon test) among the three groups, P = ,083 (log-rank) and P = ,074 (Wilcoxon) between the CWft and the control groups. and P = ,022 (log-rank) and P = ,019 (Wilcoxon) between the Uft and the control groups, which indicates higher survival

rates in the CWA and the Uft groups compared with the control group. A multivariate statistical analysis oo prognostic factors using Cox’s proportional hazards model was performed with the following results: P = ,037, hazards ratio = 0.64 with a 95% confidence interval (CI) of 0.42 to 0.97 (control v CWfl group); and P = ,009, hazards ratio = 0.55 with a 95% Cl of 0.36 to 0.86 (control v Uft group). Conclusion: Significantly favorable results were obtained in the CWft and Uft groups compared with surgery alone. These data showed significant prognostic advantages in the postoperative adjuvant chemotherapy groups.

Preoperative concurrent chemoradiotherapy for unresectable stage III nonsmall cell lung cancer Milstein D, Kuten A, Saute M, Best LA, Daoud K, Zen-AI-Deen I et al. Northern Israel Oncology Center, Rambam Medical Centec Haifa 31096. Int J Radiat Oncol Biol Phys 1996;34:1125-32.

Purpose: We carried out a Phase II trial in an attempt to improve resectability and survivability of inoperable Stage III A and III B nonsmall cell lung cancer (NSCLC) patients by implementing a neoadjuvant chemoradiotherapy treatment program. Methods and Materials: Thirty-six patients with locally advanced Stage III NSCLC received neoadjuvant therapy consisting of 50.4 Gy in 5.5 weeks concurrent with two cycles of chemotherapy, using cisplatin and etoposide. No postsurgical consolidation therapy was given. Rex&s: Assessment at 3 to 6 weeks after treatment suggested that 26 (72%) patients had been rendered resectable. Toxicities were common but usually tolerable; however, one toxic death occurred. Of 24 patients who proceeded to thoracotomy, complete resection was achieved in 20 (56%). There were two surgically related deaths. Surgical-pathological staging showed downstaging in 18 patients, including complete sterilization of the tumor in 3 (8%). The median survival for all 36 patients is IS months, but at the time of analysis, median survival of resectable patients had not been reached. The actuarial 2-year survival is 39% for all study groups, 57% for resectable patients, and 16% for the remaining (p < 0.005). Conclusions: While this preoperative neoadjuvant appears to improve survival of patients with Stage III NSCLC. comparison with previous reports of other similar trials indicate a superior survival advantage in association with higher doses of radiotherapy.

The role of adjuvant therapy in the pN2 non small cell lung cancer (NSCLC) Chella A, Lucchi M, Gragnani F, Ribechini A, Silvano G, Janni A et al. Dipartimento di Chirurgra Toracica, Universita degli Studi. Ma Roma, 67. 56100 Piss. Minerva Chir 1995;50:1029-38.

Over a period of eleven years (1983-1993), the role of adjuvant chemo and/or radiotherapy was evalutated on 222 resected patients (pts) with NSCLC at atage IIIA(N2). All the patients undenvent an attentive mediastinal limphoadenectomy. Fifty-live patients had a clinical mediastinal node involvement. 174 pts had a single media&al node station involved while 48 had two or more stations involved. One hundred and seventy-one pts (77%) underwent adjuvant therapies, consisting of citotoxic chemotherapy in 40 pts, radioterhapy in 97 pts and chemoradioterhapy in 34 pts. Follow-up lasted until September 1994. Overall 5-yr survival was 17.5%, the median being 17 months. Forty-two pts were. at that moment, still living (median 43.5 months, min 1 I-maw 120) with 37 disease free. We verified a significant dif- ference concerning survival among the three histologic types (p = 0.03). with the squamous achieving the best result (21.3% at 5-yrs). Surgical N2 had a better survival (20/5% at 5-yrs) than the clinical one (9%), @ = 0.01). In particular, if only one nodal station was involved, survival was 21.3% compared to 4.5% when metastases were present at two or more nodal station (p = 0.0001). Considering the level of mediastinal node involvement, the worst prognosis was linked to the carina node metastases (p = 0.02). Survival benefits were obtained by means of

398 Abstmcrs 1 Lung Cancer 15 (1996) 381-399

adjuvant therapies (20/2% vs 8.1%). @ = 0.0002). Analyzing all the pts, the best survival was achieved in those treated by surgery plus chemo- radiotherapy (32.4%). (p = 0.0001). As regards the squamous cell tumors, pts who underwent surgery plus radiotherapy had the best prognosis (24.2%) @ = 0.0026). Further, in non-squamous cell tumor, chemo-radiotherapy increased survival (45%). (p = 0.0001). At multivariate analysis, only the level of nodal involvement and the adjwant therapy mantained their statistical significance. Our results prompt us to conclude that: 1) Squamous cell tumors and single nodal station involvement are Linked to the best prognosis; 2) Squamous cell carcinoma should be treated by adjwant radiotherapy; 3) Non-squamous tumors should undergo to chemo-radiotherapy; 4) Clinical N2 (according to our recent experience) may benefit from neoadjuvant chemotherapy.

Long-term follow-up of a randomised trial of combined chemo- radiotherapy induction treatment, with and without mainte- nance chemotherapy in patients with small cell carcinoma of the lung Beith JM, Clarke SJ, Woods RL, Bell DR Levi JA. Department Clinical Oncoio~, Royal North Shore Hospital, St Leonards, Sydney, NSW 2065 Eur J Cancer Part A Gen Top 1996;32:438-43.

The toxicity and efficacy of concomitant chemotherapy and radiotherapy as induction therapy was evaluated in patients with previously untreated small cell carcinoma of the lung (SCLC), and in responding patients the value of maintenance chemotherapy was examined. 202 patients received induction chemotherapy with cisplatin and etoposide (EP), in combination with cranial and local radiotherapy. 85 patients (42%) developed grades III and IV myelosuppression, the main toxicity of induction treatment. Gf the 154 responding patients. 129 were randomised to maintenance chemotherapy with vincristine, doxorubicin and cyclophosphamide (VAC) or no further treatment. The response rate for the limited disease patients (LD) was 87%, 62% achieving a complete response (CR) and the response rate for extensive disease patients (ED) was 68%, with 26% achieving a CR. 17 patients (I I%) completed 10 courses of maintenance chemotherapy. 32 patients (57%) developed grade III and IV neutropenia. Median survival for all patients was 53 weeks f&D, 70 weeks; ED, 42.5 weeks). There was no significant difference in overall survival (OS) or disease-free survival (DFS) in the two randomisation arms. This study shows that EP combined with radiotherapy is an effective induction regimen in SCLC. Maintenance chemotherapy with VAC is not associated with increased survival but has significant toxicity alter such induction treatment.

A randomized study of high-dose split course radiotherapy preceded by high-dose chemotherapy versus high-dose radiotherapy only in locally advanced non-small-cell lung cancer. An EORTC Lung Cancer Cooperative Group trial Planting A, Helle P, Drings P, Dalesio 0, Kirkpatrick A. McVie G et al. Rotterdam Cancer Institute, Daniel den Hoed Kliniek, Gtvene Hiliedijk 301, 3075 E4 Rotterdam. Ann Oncol 1996;7: 139-44.

Background: The treatment results of radiotherapy in stage III ~~n-S~l-m1l lung cancer arc very poor. Several phase II studies showed that neoadjwant chemotherapy followed by radiotherapy was feasible in this patient group and suggested that treatment outcome might imPrwe. A randomized phase II study was performed addressing the response rate and morbidity of high-dose split course radiotherapy (RT) versus the same radiotherapy preceded by high-dose chemotherapy (CT) in patients with stage III non-small-cell lung cancer, Patients and methods: Seventy eligible patients were randomized in this study. CT consisted of cisplatin 100 mg/m2 days 1 and 22, and vindesine 3 mg/m’ on days Lg.22 and 29. Radiotherapy started on day 43 in the combined arm and immediately in the RT-only arm. The primary tumour and the regional nodes were treated by 30 Gy/lO fractions/2 weeks and after the split by a second course of 25 Gy/lO fractions/2 weeks. In the combined

arm a third CT cycle was planned during the split between RT courses, Results: In the CT + RT arm 34 patients were evaluable for response and toxicity and 30 patients in the RT only arm. After completion of treatment 7 patients had a complete response (2 in the CT plus RT arm, 5 in the RT alone arm) and 26 patients a partial response (13 in the CT plus RT arm, 13 in the RT alone arm) for an overall response rate of 52% (95% CI 39%-65%). Acute toxicity was worse in the combined treatment arm with grade 4 leucocytopenia in 8 patients and thrombocytopenia grade 4 in one patient. Three patients had reversible renal toxicity grade 2. There was one toxic death in the RT plus CT arm. There was no enhancement of acute or late radiation pulmonary or oesophageal toxicity. Time to progressive disease (median 30 vs. 35 weeks) and overall survival time (median 12 months) were equal in both treatment arms. Conclusion: High-dose radiotherapy preceded by high-dose chemotherapy was more toxic than radiotherapy alone and did not result in this study in any benefit in terms of response rate. time to progressive disease and overall survival,

A randomized controlled study of post-operative adjuvant therapy in non- small cell lung cancer Fukushima M, Tsushima T, lto H, Fukuda Y, Maruyama A, Fujita H et al, Lung Cancer Study Group, First Department of Surgev, Hirvsokr Univ. School of Medicrne. Hirosaki. Jpn J Cancer Chemother 1996;23:303-9.

The efficacy of postoperative adjuvant chemo and chemoimmu- notherapy in non-small cell lung cancer was evaluated in a multicentric prospective randomized study. From September 1987 to June 1990, resected lung cancer patients were randomly stratified into three groups. Group A received 2 courses of chemotherapy with CDDP and VDS following operation. Group B was administered UFI daily for 1 year after 2 courses of CDDP. Group C received intrapleural administration of OK-432 after lung resection, then UFT and OK- 432 once every 2 weeks for 1 year. Out of 94 cases, analyses were carried out on 87 of eligible cases. The five-year survival rate was 56.8% in stage I (43 cases). 73.3% in stage II (12 cases), 18.8% in stage 111 A (24 cases). 50% in stage 111 B (2 cases) and 33.3% in stage IV (6 cases). The five year survival rate in group A was 32.2%. 55.2% in group B and 53.9% in group C, and no statistical difference was recognized between 3 groups. But in the cases of noncurative resection. the 5-year survival rate was significantly low in group A compared with Group B or C Similarly, the cases with low-grade TP (< 6.0 gidl) or low response of PPD skin reaction (< 12 mm) showed a significantly low 5-year sur- vival rate only in group A. From these results. it was suspected that aggressive chemotherapy provides no benefit for postoperative lung cancer patients with advanced disease.

Other treatment modalities Killing of laminin receptor-positive human lung cancers by tumor- infiltrating lymphocytes bearing gammadelta’ T-cell receptors Ferrarini M, Heltai S, Pupa SM, Menard S, Zocchi MR. Laboratorio Immunoterapia Adottiva, Istituto Scientijico H. S. Raffaele, Ma Olgettina 60, 20132 Milan. J Nat1 Cancer Inst 1996;88:436-41.

Backgmvnd: The monomeric laminin receptor, a 67-kd high- affinity laminin- binding protein, is expressed by a variety of normal cell types. Overexpression and abnormal surface distribution of this receptor have been demonstrated in tumor cells, where it appears to promote tumor invasion and metastasis. Previously, we reported the existence of an association between laminin receptor overexpression by lung cancer cells and the presence of tumor-infiltrating lymphocytes (TILs) bearing gammadelta T-cell receptors. gammadelta’ lymphocytes represent a sizable fraction of the TILs in approximately one fourth of lung cancers analyzed thus far. Purpose: The aim of this study was to