THE THIRD INTERGROUP RHABDOMYOSARCOMA STUDY

Purpose: The ultimate goal of the Third Intergroup Rhabdomyosarcomo St udy (IRS-III, 1984 to 1991) was to improve treatment outcome in childr en with rhabdomyosarcoma through clinical trials comparing risk-based protocols of surgery and multiagent chemotherapy, with or without irra diation. Patients and Methods: One thousand sixty-two previously untre ated, eligible patients who were entered onto the study after surgery were randomized or assigned to treatment by clinical group (I through IV), histology (unfavorable or favorable), and site of the primary tum or. Initial responses, progression-free survival (PFS), and survival ( S) were the end points used in comparisons between randomized groups a nd between patients treated in IRS-lll and IRS-ll (1978 to 1984). Resu lts: The overall outcome of therapy in IRS-III was significantly bette r than in IRS-II (5-year PFS, 65% +/- 2% v 55% +/- 2%; P < .001 by str atified testing). Patients with group I favorable-histology tumors far ed as well on a 1-year regimen of vincristine and dactinomycin (VA), a s did a comparable group treated with VA plus cyclophosphamide (C) (5- year PFS, 83% +/- 3% v 76% +/- 4%; P = .18). Results for patients with group II favoroble-histology tumors, excluding orbit, head, and parat esticular sires, were inconclusive regarding the benefit from addition of doxorubicin (ADR) to VA. Patients with group III tumors, excluding those in special pelvic, orbit, and other selected nonparameningeal h ead sites, fared much better on the more intensive regimens of IRS-lll than on pulsed VAC or VAC-VADRC in IRS-II (5-year PFS esti motes, 62% +/- 3% v 52% +/- 3%; P < .01); however, there were no significant dif ferences in outcome among the groups treated in IRS-III. patients with metastatic disease at diagnosis (clinical group IV) did not benefit s ignificantly from the more complex therapies evaluated Conclusion: Int ensification of therapy for most patients in IRS-III, using a risk-bas ed study design, significantly improved treatment outcome overall. The largest gain from this strategy was realized in patients with gross r esidual tumor after biopsy (clinical group III). It was also possible to decrease therapy for selected patient subsets without compromising survival. (C) 1995 by American Society of Clinical Oncology.