Is concomitant cisplatin and radiotherapy more efficacious treatment than radiotherapy alone in stage III non-small cell lung cancer?

Abstract

In this Journal, Trovo et al. (7) reported a randomized study to test an efficacy of concomitant cisplatin and thoracic radiotherapy (TRT) in Stage III non-small cell lung cancer (NSCLC). One hundred and seventy three patients were randomized to receive TRT 45 Gy in 15 fractions over 3 weeks (Arm A) or same TRT with concomitant low-dose continuous cisplatin (6 mg/m2) (Arm B). There was no significant difference between the arms in response, progression-free interval, survival, or patterns of failure. Their patient population was, perhaps, so unfavorable that possible differences between the arms were obscured, whereas CALGB studied a more favorable patient population with AJCC Stage III NSCLC (2). Stage III by the UICC classification used lumps together a very heterogeneous group of patients which have partially been separated in more recent classifications (4). Half the patients had Karnofsky Performance Status (KPS) score of 5 80, and up to 10% weight loss was permitted. Cox et al. ( 1) found that the inclusion of patients with very advanced primary tumors, KPS 5% obscured a dose response from 60 Gy to 69.6 Gy with hyperfractionated radiation therapy. Their endpoints of response and median survival are not predictive of 2-5 year survivals. Schaake-Koning et al. (5) found little difference in the median survivals of three groups (TRT alone, TRT + daily cisplatin and TRT + weekly cisplatin) but 3-year survivals were significantly improved by giving concomitant daily or weekly cisplatin compared to TRT alone group. The other two groups received same TRT combined with concomitant cisplatin, 30 mg/m2 given on the first day of each treatment weekly; or 6 mg/m2 of cisplatin given daily before radiotherapy. This study also showed highly significant improvement in local-regional control in the radiotherapy and cisplatin groups as compared with the radiotherapy alone. The improved local control with cisplatin was associated with better survivals. However, their daily cisplatin group had a 16% 3-year survival which was compared to 2% in the TRT alone group. The TRT alone group received a split course of radiotherapy (3 Gy X 10 fractions/ 3-4 week break followed by 2.5 Gy X 10 fractions) which may have resulted in a lower survival rate than similar or higher total doses with a split. Actually Trovo’s radiotherapy alone group had a 10% 3-year survival rate by giving 3 Gy X 15 fractions over 3-weeks without break. This rapid completion of radiation therapy might be more effective than more prolonged radiotherapy. An international workshop was held in Fontainbleau, France, in June, 1992, under the auspices of the International Association for the Study of Lung Cancer (IASLC) to discuss combined modality treatment of lung cancer. Dr. Trovo was an active participant. The consensus was that there have been too many anecdotal and inadequately designed studies regarding treatment of Stage III NSCLC. It is necessary to distinguish different staging systems and subsets within Stage III, clinical or surgical staging, pretreatment patient characteristics (performance status, weight loss, and age). Randomized Phase III trials must be conducted with enough patients treated in the study, adequate duration of follow-up, and experimental treatments compared to well-treated controls (6). Although randomized studies have been criticized (3) little with benefit has come from small, uncontrolled studies. All workshop participants agreed it is important to be more open to improving the quality of randomized studies rather than criticizing them and failing to participate in them. The trial of Dr. Mauro Trovo and his colleagues was praised, at least for its conduct, if not its results.