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Phase III Trial To Preserve The Larynx: Induction Chemotherapy And Radiotherapy Versus Concomitant Chemoradiotherapy Versus Radiotherapy Alone, Intergroup Trial R91-11

Diana Stripp, MD

University of Pennsylvania Cancer
Last Modified: May 14, 2001

Presenter: Arlene A. Forastiere
Affiliation: Intergroup

Background:

1. Induction chemotherapy (IC) followed by radiation has been the standard of treatment for advanced laryngeal carcinoma.
2. In the landmark study of the VA laryngeal trail. (NEJM 324:1685, 1995), induction chemotherapy using cis-platinum (cDDP) and 5-Fu followed by radiation show preservation of larynx ins 64% of surviving pt with no difference in survival compared with pt treated with definitive surgery.

Materials and Methods:

1. 547 pts with stage III&IV potentially resectable cancer of the larynx were randomized to receive: Arm A-IC cDDP+ 5-FU (CF) for 3 cycles followed by RT in responding pts, Arm B- concurrent cisplatin(C) on days 1,22,43 and RT or Arm C- RT alone.
2. RT total dose was 70 Gy in 7 wks, 2 Gy/fx for all three arms.
3. Arm A served as the control; the primary endpoint was laryngectomy-free survival(LFS).

Results:

1. Of the 510 analyzable patients, characteristics were balanced in all 3 arms.
2. 81% arm A completed IC compared to 65% arm B completed 3 cycles of cDDP.
3. Radiation completion: arm A 84%, B 91% and C 95%.
4. Medium follow up was 30 mos
5. Toxicity was highest in the concurrent chemotherapy and radiation arm (B).
6. There is no significant difference in overall survival comparing Arms B or C to control Arm A.
7. Laryngeal preservation was highest in Arm B: 74% arm A vs 88% arm B vs 69% in C
8. Time to laryngectomy(TTL) is significantly better for Arm B compared to Arm A, p=.0094. Secondary analysis comparing Arm B to Arm C demonstrates a significant difference in LFS (p=.02) and TTL (p=.00035).
9. Suppression of distant metastasis was seen in 93% in both arms that received chemotherapy

Authors' Conclusions

1. Induction chemotherapy followed by XRT has no advantage over RT alone in laryngeal preservation.
2. Concurrent chemoradiotherapy provides significant improvement in the rate of laryngeal preservation over the IC arm with significant increases in the TTL.
3. Chemotherapy provides systemic effect by surpressing rate of distant metastasis.
4. High rate of larygeal preservation with concurrent chemoradiotherapy provides new standard in this group of pts. Clinical/Scientifuic implications: (include clinical and scientific implications of findings)

Clinical/Scientific Implications:

1. Concurrent chemoradiation provides high rate of laryngeal preservation with ga considerable increased in toxicity. Sufficient supportive care during the treatment is essential, especially in this group of patients where compliance and social support are often an major issue.
2. Concurrent chemotherapy and radiation therapy is a resonable option in patients with excellent performance status who are highly motivated to preserve the larynx.