Long-term benefit is observed in a phase III comparison of sequential vs concurrent chemo-radiation for patients with unresected stage III nscls: RTOG 94-10
Reviewer: Ryan Smith, MD
Last Modified: June 1, 2003
Presenter: W.J. Curran Presenter's Affiliation: RTOG Type of Session: Scientific
There has been a demonstrated survival benefit of chemoradiation over radiation alone in stage III non-small cell lung cancer (NSCLC)
This survival benefit has been demonstrated in several studies using sequential chemotherapy followed by radiation therapy.
The EORTC and CEBI showed an advantage of concurrent chemotherapy with radiation therapy.
This study was performed to detemine which approach is best
Materials and Methods
610 patients were accrued over 4 years, with 595 evaluable
All had stage IIIA/IIIB or medically inoperable stage II disease, with a KPS >= 70 and weight loss <= 5%
Patients were randomized between 3 arms:
Arm 1: SEQ-vinblastine 5 mg/m2/wk x 5 + cisplatin 100 mg/m2 days 1, 29 with radiation to 60 Gy (2 Gy per day) beginning on day 50
Arm 2: CON-vinblastine 5 mg/m2/wk x 5 + cisplatin 100 mg/m2 days 1, 29 with radiation to 60 Gy (2 Gy per day) beginning on day 1
Arm 3: BID-oral etoposide 50 mg BID x 10 weeks + cisplatin 50 mg/m2 days 1, 8, 15, 29, 36 with radiation to 69.6 Gy (1.2 Gy BID) beginning on day 1
Median follow-up time was 6 years, with minimum follow up of 4 years (therefore all results reported are actual-not actuarial)
75% of patients had KPS of 90-100 and just over 50% were stage IIIB
Median survival time was 14.6 mo, 17.0 mo, and 15.2 mo for Arms 1, 2, and 3, respectively
4 year overall survival was 12%, 21%, and 17% for Arms 1, 2, and 3, respectively
This corresponded to a survival benefit, with Arm 2 compared to arm 1 (p=.046)
Acute toxicity was much higher in arms 2 and 3, most notably for grade 3-4 esophagitis (4% (Arm 1), 25% (arm 2), and 47% (arm 3))
There was no difference in acute pneumonitis rates (7%, 4%, 3%)
There was a low level of late esophageal toxicity in all groups (1%, 2%, 3%)
There was no difference in late pneumonitis between the groups, though this rate was higher than expected (13%, 11%, 13%)
Concurrent chemoradiation had a significantly better survival when compared to sequential chemoradiation treatment
This concurrent treatment did confer a greater acute toxicity, but this did not result in any increased late toxicity
Arm 3 (BID radiation) had a much higher acute toxicity rate than the other arms, but without any additional survival benefit
Concurrent chemoradiation should now be considered the standard of care in stage III and inoperable NSCLC
Locally advanced NSCLC remains a challenging disease to treat, with the majority of patient still failing and succumbing to their disease. Starting with the Dillman trial, published over a decade ago, it has been shown that chemoradiation has a benefit over radiation alone. This study now defines the use of concurrent chemoradiation in this group of patients. This study shows an overall survival benefit with concurrent chemoradiation over radiation alone. However, patient selection will remain key, as this study enrolled only those patients with an excellent performance status and virtually no weight loss. This practice should continue to be employed, especially given the high rate of esophageal (and hematopoetic) toxicity as well as the surprisingly higher rate of late lung toxicity. However, this study, paired the Furuse study (which showed a 17% survival vs a 10% survival in terms of concurrent and sequential chemoradiation, p=.04) proves that concurrent chemoradiation should be the standard of care in good performance status patients with inoperable NSCLC.
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