Absrructs / Lung Cancer 12 (1995) II3-160

Concerning Grade 2 or 3 nausea and vomiting, good conditions were observed on day 1 (day of treatment), most marked aggravation on day 2, and initiation of improvement on day 4. Vomiting was slight on day 1, most aggravated on day 2, but began to improve on day 3; good results were generally observed thereafter. Decreased appetite was slight oo day 1, but was most aggravated on day 3 and 4; its recovery was delayed even until day 7. In the treatment for delayed emesis, comparison was made among the group treated with granisetron alone who did not require treatment for delayed emesis, the group with delayed emesis treated with granisetron, and the group with delayed emesis treated with drugs other than granisetron. Slightly better results were observed in terms of nausea, vomiting, and the frequency of vomiting in the group treated with granisetron alone on days 2 and 3. However, no significant difference was observed in decreased appetite among the 3 groups. Granisetron had no side effects and was safe. It inhibited vomiting, but measures to improve decrease appetite are needed.

Activity of docctaxel (Taxoterr) in small cell lung cancer Smyth JF. Smith lE, Sessa C, Schoffski P, Wanders J, Franklin H et al. Univ. Department Clinical Oncology Western Generai Hospital, Edinburgh EX4 2XU Eur I Cancer Part A Gen Top 1994;30:1058&0 Docetaxel (Taxoterc) is a new cytotoxic compound with a broad spectrum of activity in preclinical studies. This paper reports a phase II trial in patients with previously-treated small cell carcinoma of the lung. 34 patients received 100 rig/m’ of doaztaxel in an intravenous infusion given over I h every 21 days. Seven partial responses were reported (25% of 28 evaltile patients). Duration of response was 3.5-12.6 months. Toxocities were predominantly neutropenia, alopecia and asthenia. Docetaxel is a new compound with activity in previously- mated patients with small cell lung cancer, and is suitable for evaluation in combination with other cytotoxic drugs active in this disease.

Platinum-based chemotherapy in non-small cell lung cancer: The experience of the European Organization for the Reseamb and Treatment of Cancer Van Zandwijk N, Dalesio 0. Department of Pulmonary Oncology, Netherlands Cancer Institute. Antoni van Leeuwenhoek Huis. Plesmaniaan 121, 1066 CXAmsterdam. Semin Oncol 1994;21:Suppl 6:66-71. The history of chemotherapy for non-small cell lung carcinoma is one of very slow progress. Consequently, the categories of patients who will ultimately benefit from this modality are still debated. Recent European Organization for Research and Treatment of Cancer studies show that there is less concern about the importance of platinum as an ingredient of combination regimens or as an adjunct to radiotherapy. The presence of cisplatin is related to better response and smvival in patients with locoregional and distant me&static disease.

Small cell lung cancer in the elderly Byrne A, Carney DN. Department of Medical Oncology, Mater Misericordiae Hospital, Eccles St, Dublin 7. Semin Oncol 1994;21:Suppl 6:43-8 Mortality rates for patients with lung cancer remain high, despite advances both in our understanding of lung cancer biology and in smvivd statistics for other types of cancer. Important strategies for improving the figures for lung cancer are identification of subgroups at highest risk for the disease and targeting high-intensity therapy to patients with the greatest chance for cure. In this context, special attention must be given to the elderly population, which accounts for

approximately 60% of all cancer cases. Recognizing that close to 13% of the population of the United States can be considered elderly and that this figure is expected to more than double over the next 40 years, the elderly cohort clearly has a significant impact on cancer statistics in general. While approximately 26% of lung cancer patients are potentialIy curable, the 74% majority has only a remote chance of being cured of their disease. More active therapeutic modalities, with a meaningful effect on survival and quality of life but with more acceptable toxicity than intensive therapy designed for patients with a good chance of cure, are clearly needed for these patients. Several studies have demonstrated that use of oral active agents such as etoposide, alone or in combination with other agents, produce an overall response rate and median survival time similar to those of the more intensive schedules. Once further studies clarify the optimum schedule for use of oral etoposide, it is hoped that its use in combination with other therapeutic agents and/or with radiation therapy will improve the overall response and survival rates among patients at high risk or with poor prognostic factors, such as the elderly.

Etoposidelvincristioe-based chemotherapy with or without carboplatin in extensive-stage small cell lung cancer: A prospective randomized phase III trial Gatzemeier U, Pawel JV, Laumen R, Hossfeld DK, Neuhauss R. Department of Thoracic Oncology, PneumologyRhoracic Surgery CenteK Grosshansdorf Hospital, D 2070 Gmsshansdorf/Hambutg Semin Oncol 1994;21:Suppl6:31-5. In the treatment of small cell lung cancer, carboplatin/etoposide/ vincristine (CEV) is one of the most active regimens. In contrast, the etoposidelvincristine (EV) combination also has produced acceptable results in patients with extensive disease. To evaluate the efflcaicacy and survival of patients treated with EV in comparison to those treated with more intensive CEV chemotherapy, a prospective, randomized, phase III trial was performed. The protocol for the treatment groups was as follows: treatment A (156 patients): carboplatin 300 mg/mz day I, etoposide 140 mplm2 days 1 through 3, and vincristine 1.4 mg/m2 days 1.8, and 15; and treatment B (16 1 patients): etoposide 200 mg/m’ days 1 through 3 and vincristine 1.4 mp/m’ days 1 and 8. Chemotherapy cycles in each treatment arm were repeated every 4 weeks. Doses were reduced by 20% when hematologic or nonhematologic toxicity (grade 4) occurred. In all, 317 evaluable patients were treated. The overall response rate for patients treated with CEV was 79.8% compared with 59.8% for those treated with EV (P < ,001). The median length of survival was 10 months for CEV-treated patients compared with 9 months for EV-treated patients (P = .19). Based on long-term survival rates, there was an advantage for the CEV-treated patients if they had good performance status, were younger than 60 years, had no distant metastases, and achieved a complete response to first-line therapy. We conclude that patients with poor prognostic factors (ie, poor performance status, multiple distant metastases, and less than partial response to the first cycle of chemotherapy) should appropriately be treated with the less aggressive two- drug combination chemotherapy. On the other hand, patients with good prognostic factors should be treated as aggressively as possible, and they will benefit from the more aggressive induction chemotherapy.

Cisplatin/etoposide versus carboplatinktoposide chemotherapy and irradiation in small cell lung cancer: A randomized phase III study Kosmidis PA, Samantas E, Fountzilas G, Pavlidis N, Apostolopoulou F. Skarlos D. Department of Medical Oncologv. Metaxa Cancer Hospital, Botassi 51, Piraeus. Semin Oncol 1994;21:Suppl6:23-30. The efficacy and toxicity of cisplatin/&poside and carboplatinletoposide combinations along with thoracic irradiation were pmspectively assessed

Abstracts/Lung Cancer I2 (1995) 113-160 147

in patients with small cell lung cancer. Both combinations were equally effective. However, the carboplatinletoposide regimen caused significantly leas nausea, vomiting, nephrotoxicity, and neurotoxicity, and it was easier to administer. Dose intensity and treatment delays were similar in both groups. Thoracic irradiation given concurrently with chemotherapy is feasible and seems to offer a survival advautage. The relapse rate also is lower among patients who have received radiation therapy, and recurrences tended to be outside of the lung. Gverall, a survival benefit was identified for patients aged between 50 and 65 years who had limited disease, good performance status, and only one metastatic site. Prophylactic brain irradiation in a subset of patients reduced brain metastasis, but the difference did not reach signiticance. From this trial, it is concluded that carboplatinktoposide combination therapy is highly effective and is well tolerated by patients with small cell lung cancer. In limited disease+, this combination can be given concurrently with thomcic irradiation and offers a survival advantage.

Carboplatin for small cell lung cancer: Progress toward greater efficacy and reduced toxicity Raghavau D. Perez R. Creaven P Takita H. Loewen G. Vaickus L. Department of Medicine, Roswell Park Cancer Institute, Elm and Car&on Sts, Buffalo, NY 14263. Semin Gncol 1994:21 Suppl6:1-8. Small cell lung cancer, an aggressive malignancy characterized by early dissemination, is highly responsive to radiotherapy and cytotoxic chemotherapy. Since. the introduction of combined-modality regimens that incorporate both radiotherapy and chemotherapy, the median survival time for patients with localiied disease has increased to 12 to 15 months, but median length of survival of patients with extensive disease has remained at a plateau of only 6 to 8 months. New cytotoxic agents, such as ifosfamide, etoposide, and carboplatin, have contributed to a reduced toxicity profile and an increase in complete response rates to combination regimens of 40% to SO%, hut they have not contributed to any major increase in long-term survival. Potential strategies for improving efficacy and reducing toxicity of the chemotherapy of small celi lung cancer are reviewed.

Etoposide in the treatment of elderly/poor-prognosis patients with small-cell lung cancer Camcy DN, Byrne A. Mater Misericoniiae Hospital, EC&S Street, Dublin 7. Cancer Chemother Pharmacol Suppl. 1994,34:S96-SIOO. Survival rates for cancer have improved in recent decades, specifically for younger patients. However for those over 65, who account for over half of all cancer patients, mortality rates remain poor. In those with small-cell lung cancer the achievement of cure is possible in only a minority (5-10%). For the elderly and those with extensive disease we have found that the use of oral etoposide offers similar survival rates to more intensive regimens, with minimal side effects and hospitalisation. Thus the expansion of the elderly population mandates for more specific chemotherapeutic approaches in this group.

Alpha interfemn, leucovorin, and S-fluorouracil (ALP) in advanced cancer: Results of a dos&nding study and evidence of activity in non-small cell lung cancer Quan WDY Jr, Madajewicz S, Smith MR, Skeel RT. Division of Hematology/Oncology Department of Medicine, Medical ColIege of Ohio, 3000 Arlington Avenue, Toledo, OH 43699. Cancer Invest 1994;12:367-74. In a phase I trial, 17 patients were treated with 5-fluorouracil(5-PU) 500 m&m2 and Ieucovorin (LV) 500 mg/m’ intravenously weekly for 6 weeks followed by 2 weeks’ rest and interferon alfa-2b 1, 3,5,8, or 10

million units (MU) suhcutanwusly tiw with no rest period. The most wmmon toxicities were fatigue (12). diarrhea (lo), nauseahomiting (7) and fever (7). The maximum tolerated interferon dose was 8 MD tiw. Fatigue and increased incidence of other toxicities rather than a single dose-limiting toxicity occurred at the next highest interferon level. ECGG grade III/IV toxicity occmred in 5 patients and included transient supmventricular tachycardia and brief seizure episode(l), dyspnea (I), decreased performance status (1) anemia requiring tramfusion (l), and deep vein thrombosis (1). No toxic deaths cccurred. Two patients with non-small cell lung cancer (NSCLC) had partial responses lasting 5 and 4 months. lko other patients with NSCLC had either minor Rsponse or stable disease, and 1 patient with colon cancer had a significant decline in serum CEA. The recommended alpha interferon dose is 8 MU tiw when given with this schedule of 5-FLPLV.

Phase II study of fotemustiae in untreated inoperable non-small- cell lung cancer Rudd R, Allen R, Berille J, Spiro SG, Tmsk C, Souhami RL. Department Oncologv/lRespiratoty Med., Univ. College London Medical School, Middlesex Hospital, London WINBAA. Cancer Chemother Phannacol 1994;34:444-6. A total of 43 patients with advanced, previously untreated non-small- cell lung cancer (NSCLC) were treated with a novel nitrosourea, fotemustine, given at 100 mp/m’ on days 1 and 8. Maintenance treatment consisted of a single injection of 100 mg/m* given every 21 days. 37 patients were evahiable for respone. Gf these, 5 patients had a partial response (13.5%; 95% confidence interval, 6%-28%). Toxicity comprised mairdy anaemia and thrombocytopenia. other toxicities were mild. This phase II study wntirms that fote.mustine is a moderately active and well-tolerated drug in NSCLC.

Exterual radiotherapy for Pancoast tumor Hayashi S, Sekiguchi K, Nakazawa M, Sougawa M, Yamashita T. Deparrinent of Radiology. Jichi Medical School, Kawachi-gun 329-04 Lung Cancer (Japan) 1994;34:347-54. From January 1981 to December 1992,248 patients with non-operable non-small cell lung cancer were treated by external radiotherapy (RT). Among these, 10 patients had Paucoast tumor with UICC clinical stage III (s8) and IV (n=2) disease. Symptomatic relief, tumor response and survival were analyzed. As for initial symptoms, regional pain was observed in all patients, with arm pain being especially frequent (8110). Numbness was prcscnt in 5, Homer’s syndrome in 2, muscular atrophy of the hand in 2 patients. Pain was relieved in 7 patients (70%) and the median duration was 8.5 months, On the other hand, numbness and Homer’s syndrome did not improve at all. Nine cases were evaluated for response to radiotherapy. ‘Iwo patients receiving a dose of more thau 65 Gy achieved a partial response One patient is still alive over 5 years. The other 7 patients showed no response. The median survival for stage III patients was 13.6 months and the J-year actuarial survival rate was 3 1%. Mild radiation pneumonitis was seen in one case and arm swelling in another, at 3 months and 4 years after RT, respectively. External RT with curative intent for Pancoast tumor was etfective for pain relief and appeamd to prolong survival when high doses wuld be administered, using the shrinking field technique.

A randomized controlled postoperative adjuvant cbemotberapy trial of CDDP + VDS + UFT and IJm alone in compahoa with operation only for non-small cell lung carcinomas - Second study Tomita M. Lung Cancer (Japan)1994;34:297-306, A multi-institutional cooperalive study was carried out in Western Japan to examine the smvival periods and side effects of postoperative adjuvant