RTOG 91-11 / Intergroup (1992-2000) -- Sequential chemo -> RT vs. concurrent chemo-RT vs. RT alone
Randomized, 3 arms. 518/547 patients. Stage III or IV cancers of the glottic or supraglottic larynx, which would require total laryngectomy. Excluded T1 and large volume T4 (penetrating through cartilage or >1cm into BOT). Arm 1) Induction cisplatin 100 mg/m2 + 5-FU C.I. 1000 mg/m2 Q3W x3 cycles, followed by RT (if CR or PR) or laryngectomy if poor response (this Arm based on results of the VA Larynx trial) vs. Arm 2) Concurrent cisplatin 100 mg/m2 Q3W + RT vs. Arm 3) RT alone. RT dose was 70/35, elective neck and SCV 50/25. Patient in the first arm who had salvage surgery for poor response to chemo received adjuvant RT to 50-70 Gy depending on surgical margin status. Planned lymph node dissection was performed for LN > 3cm or multiple lymph nodes at original staging. In induction group, 83% continued to RT and most of others received more chemotherapy or RT but not surgery. End point was preservation of larynx
4-years; 2003 - PMID 14645636 — "Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer." (Forastiere AA et al. N Engl J Med. 2003 Nov 27;349(22):2091-8.) Median F/U 3.8 years
Larynx preservation: induction 72% (SS) vs. concurrent 84% vs. RT alone 67% (SS). No benefit to induction chemo over RT alone. Laryngectomy-free survival at 2-years and 5-years was 59%/43% (induction), 66%/45% (concurrent), and 53%/38% (RT alone), with no S.S. difference between the two chemo groups but a S.S. difference between concurrent and RT alone. There was no difference in LFS between the two chemo arms due to an increase in intercurrent deaths for the concomitant group.
Speech & swallow: 2-year moderate+ impediment induction 3% vs. concurrent 6% vs. RT alone 8% (NS)
Outcome: 2-year OS induction 76% vs. concurrent 74% vs. RT alone 75% (NS). 5-year OS 55% vs. 54% vs. 56% (NS). LC 64% (SS) vs. 80% vs. 56% (SS), no benefit for induction over RT alone. DM induction 9% vs. chemo-RT 8% vs. RT alone 16% (SS)
Toxicity: Grade 3-4 induction chemo 24% vs. concurrent chemo 30% vs. RT alone 36% (NS); treatment-related deaths 3% vs. 5% vs. 3%
Conclusion: Larynx preservation best with concurrent chemo; distant mets reduced by chemotherapy.
Salvage Laryngectomy; 2003PMID 12525193 — "Outcome of salvage total laryngectomy following organ preservation therapy: the Radiation Therapy Oncology Group trial 91-11." (Weber et al. Arch Otolaryngol Head Neck Surg. 2003 Jan;129(1):44-9.)
Outcome: Total laryngectomy induction 28% vs. concurrent 16% vs. RT alone 31% (SS). Complication rate 52-59% (NS), pharyngocutaneous fistula 15-30%. LRC 74% vs. 74% vs. 90%. 2-year OS 69% vs. 71% vs. 76% (NS)
Conclusion: Laryngectomy following organ preservation treatment has acceptable morbidity. Survival not influenced by initial organ preservation strategy
5-years; 2006ASCO Abstract -- "Long-term results of Intergroup RTOG 91-11: A phase III trial to preserve the larynx--Induction cisplatin/5-FU and radiation therapy versus concurrent cisplatin and radiation therapy versus radiation therapy." (Forastiere AA, Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 5517)
Outcome: 5-year laryngectomy-free survival I+RT 45% vs CRT 47% vs. RT 34% (SS). Laryngeal preservation 70% vs. 84% vs 66% (SS). LRC 55% vs 69% vs 51% (SS). CRT significantly better than I+RT or R. DM low 14% vs. 13% vs 22% (NS). OS 59% vs. 55% vs. 53% (NS)
Conclusion: Concurrent chemo-RT superior treatment in terms of larynx preservation and locoregional control, but no difference in 5-year overall survival
RTOG 91-11 / Intergroup (1992-2000) -- Induction chemo -> RT vs. concurrent chemo-RT vs. RT alone
Randomized, 3 arms. 518/547 patients. Stage III or IV cancers of the glottic or supraglottic larynx, which would require total laryngectomy. Excluded T1 and large volume T4 (penetrating through cartilage or >1cm into BOT). Arm 1) Induction cisplatin 100 mg/m2 + 5-FU C.I. 1000 mg/m2 Q3W x3 cycles, followed by RT (if CR or PR) or laryngectomy if poor response (this Arm based on results of the VA Larynx trial) vs. Arm 2) Concurrent cisplatin 100 mg/m2 Q3W + RT vs. Arm 3) RT alone. RT dose was 70/35, elective neck and SCV 50/25. Patient in the first arm who had salvage surgery for poor response to chemo received adjuvant RT to 50-70 Gy depending on surgical margin status. Planned lymph node dissection was performed for LN > 3cm or multiple lymph nodes at original staging. In induction group, 83% continued to RT and most of others received more chemotherapy or RT but not surgery. End point was preservation of larynx
4-years; 2003 - PMID 14645636 — "Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer." (Forastiere AA et al. N Engl J Med. 2003 Nov 27;349(22):2091-8.) Median F/U 3.8 years
Larynx preservation: induction 72% (SS) vs. concurrent 84% vs. RT alone 67% (SS). No benefit to induction chemo over RT alone. Laryngectomy-free survival at 2-years and 5-years was 59%/43% (induction), 66%/45% (concurrent), and 53%/38% (RT alone), with no S.S. difference between the two chemo groups but a S.S. difference between concurrent and RT alone. There was no difference in LFS between the two chemo arms due to an increase in intercurrent deaths for the concomitant group.
Speech & swallow: 2-year moderate+ impediment induction 3% vs. concurrent 6% vs. RT alone 8% (NS)
Outcome: 2-year OS induction 76% vs. concurrent 74% vs. RT alone 75% (NS). 5-year OS 55% vs. 54% vs. 56% (NS). LC 64% (SS) vs. 80% vs. 56% (SS), no benefit for induction over RT alone. DM induction 9% vs. chemo-RT 8% vs. RT alone 16% (SS)
Toxicity: Grade 3-4 induction chemo 24% vs. concurrent chemo 30% vs. RT alone 36% (NS); treatment-related deaths 3% vs. 5% vs. 3%
Conclusion: Larynx preservation best with concurrent chemo; distant mets reduced by chemotherapy.
