VA Larynx Trial (1985-1989) - Total laryngectomy + postop RT vs. induction chemo + RT
Randomized. 332 patients. Stage III or IV (excluding T1N1) cancer of the glottic or supraglottic larynx (63% supraglottic). Arm 1) Classic wide-field total laryngectomy, regional LND + postop RT vs. Arm 2) Induction chemo (cisplatin 100 mg/m2 + 5-FU 1000 mg/m2 Q3W x3 cycles) + radical RT. If not at least a PR to chemo after 2nd cycle, underwent surgery and post-op RT. Primary RT 66-76 Gy and neck 50-75 Gy depending on nodal size. Assessed 12 weeks after RT and had salvage laryngectomy if residual disease in larynx or neck dissection for residual nodal disease. Postop RT 50 Gy to microscopic disease, 60 Gy to high risk areas, and 65-74 Gy to residual disease.
2-years; 1991PMID 2034244 — "Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer." (The Department of Veterans Affairs Laryngeal Cancer Study Group. N Engl J Med. 1991 Jun 13;324(24):1685-90.) Median F/U 2.7 years
Outcome: 2-year OS chemo-RT 68% vs surgery+RT 68% (NS); DFS (NS) but but pattern of recurrence differed, with more recurrence at the primary site (12% vs 2%) in chemo/RT group vs more distant mets in surgery group (17% vs 11%).
Larynx preservation: Overall 64%. Laryngectomy 18% after induction alone, 11% after induction + RT for persistent tumor, 7% for recurrent tumor (majority within 1st year). Salvage laryngectomy T3 29% vs. T4 56% (SS), Stage III 29% vs. Stage IV 44% (SS)
Conclusion: Induction chemotherapy and radiation can be effective in preserving larynx, without compromising survival
3-years; 1993PMID 8221647 -- "Recent advances in head and neck cancer--larynx preservation and cancer chemoprevention: the Seventeenth Annual Richard and Hinda Rosenthal Foundation Award Lecture." (Hong WK, Cancer Res. 1993 Nov 1;53(21):5113-20.)
Nice overview of larynx preservation history. 3-year outcome induction chemo 56% vs. surgery-RT 53% (NS). Survival for patients who failed induction chemo and underwent laryngectomy (18%) comparable. Larynx preservation 62%, improved swallowing.
No difference in survival at 10 years of follow-up. (later paper)
