CTRT 99/97 A Randomized Trial of Simultaneous Paclitaxel and Radiotherapy vs. Radiotherapy Alone Following Induction Chemotherapy in Stage III Inoperable NSCLC

English

Reviewer: Neha Vapiwala, MD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 20 de octubre del 2003

Presenter: Jochen Willner, MD
Presenter's Affiliation: BROCAT
Type of Session: Scientific

Background

Combined modality chemoradiation is accepted in today's oncologic community as an effective treatment option for unresectable Stage III NSCLC patients, based on the demonstration of a small but significant survival advantage in several phase III randomized studies. However, the search for optimal chemotherapy and radiation regimens has continued to spawn new clinical trials. These studies have addressed issues of modality sequencing (ie: sequential vs. concurrent chemotherapy and radiation), as well as selection of the most effective chemotherapy agent(s). The "classic" chemoradiation regimen that established the efficacy of cisplatin-based induction chemotherapy followed by external thoracic radiation to 60 Gy was first reported by the CALGB (Dillman et al.) The present study builds upon this traditional approach and evaluates the use of induction chemotherapy with a platinum-taxane combination, followed by either concurrent chemoradiation or radiation alone.

Materials and Methods

Prospective randomized multicenter trial involving 20 German institutions
Study closed to accrual in 4/2002.
Patients:
- 303 enrolled
- 258 male, 45 female
- 13% Stage IIIA, 87% Stage IIIB
- Mean age = 61.5 yrs
- Mean Karnofsky performance score = 89%
- Histology = 58% squamous
All patients received induction chemotherapy consisting of 2 cycles of Carboplatin (AUC=6) and Paclitaxel (200 mg/m2) every 3 weeks.
275 patients completed induction chemotherapy.
Patients then re-staged. Operable patients (n=9)sent to surgery. Those with progressive disease (n=38) excluded from remainder of study.
219 patients with complete/partial response or stable disease were then randomized to either:
1. (n=115) 60 Gy radiation using 3-D conformal techniques
2. (n=104) same radiation with weekly low dose Paclitaxel (60 mg/m2)

NOT analyzed on an intent-to-treat basis because paclitaxel not considered standard of care in Germany.

Results

Median follow-up = 20 mos
Arm I (RT alone) vs. Arm II (RT + paclitaxel):
- Median Disease-Free Survival (DFS) 5.9 mos vs. 11.4 mos
- Median Overall Survival (OS) 14.1 mos vs. 18.7 mos
- Toxicity -- Esophagitis 6.5% vs. 12.8%
- Response Rates
  - complete 5.5% vs. 13.5%
  - partial 34.9% vs. 38.2%
  - progressive disease 44% vs. 31.5%

Author's Conclusions

Toxicity profile of combined radiation and low-dose weekly paclitaxel following induction chemotherapy is acceptable.
The DFS and remission rates appear to be better with induction chemotherapy followed by radiation and paclitaxel as compared to radiation alone.
A survival advantage is expected based on study results thus far.

Clinical/Scientific Implications

The optimum regimen of non-surgical treatment for locally advanced NSCLC patients is an ongoing quest. It has been shown that concurrent chemoradiation improves median survival compared to sequential administration in patients who are able to tolerate the regimen. This study by the BROCAT group is investigating the role of combining the sequencing concepts by incorporating chemotherapy both before AND during thoracic irradiation. The design of the experimental arm tested here was based on a prior paclitaxel dose-escalation study performed by the same investigators, demonstrating acceptable toxicity and 2-yr survival of ~60% using up to 60 mg/m2 of paclitaxel. Based on the results presented thus far, the addition of paclitaxel to radiation appears to achieve superior results compared to radiation alone. The acceptable toxicity profile further makes this regimen a plausible one, and may in fact lead to changing paradigms in treatment of this patient population. Nonetheless, the results presented here are not based on intent-to-treat analysis, which is typically considered the "gold-standard" of statistical data evaluation. This may warrant further studies in the future to validate the promising findings demonstrated here.

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