VAC and VAI or VIE with surgery (with or without RT), are equally effective for patients with local or regional rhabdomyosarcoma and are more effective for embryonal tumors than therapies used previously. Younger patients with group 1 paratesticular embryonal tumors and all patients with group 1/2 orbit or eyelid tumors can usually be cured with VA chemotherapy along with postoperative RT for group 2 disease.

Background. Intergroup Rhabdomyosarcoma Study (IRS)‐II, (1978–1984) had the general goals of improving the survival and treatment of children with rhabdomyosarcoma (RMS). Methods. Nine hundred ninety‐nine previously untreated eligible patients entered the study after surgery and were randomized or assigned to therapy by IRS Clinical Group (I‐IV), tumor site, and histologic type. Outcomes were compared between treatments and with results of IRS‐I (1972–1978). Results. Patients in Group I, excluding extremity alveolar (EA) RMS, were randomized to standard vincristine (V), dactinomycin (A), and cyclophosphamide (C) or standard VA. At 5 years, disease‐free survival (DFS) and survival (S) rates were similar between VAC and VA (DFS:80%, 70%, P = 0.47; S:85%, 84%, P = 0.73). Patients in Group II, excluding EA RMS, received radiation and were randomized to intensive VA or repetitive‐pulse VAC. Outcomes were similar for rates of DFS (69%, 74%, P = 0.83) and S (88%, 79%, P = 0.17). Patients in Group III, excluding certain pelvic tumors, received radiation and were randomized to repetitive‐pulse VAC or repetitivepulse VAdrC‐VAC (Adr, Adriamycin [doxorubicin]). Complete remission (CR) rates were close at 74%, 78%, respectively (P = 0.32), as were percentages in CR (73%) and S (66%) rates; the latter outcomes were significantly better than IRS‐I (CR: 56%, P < 0.001; S:50%, P < 0.001). Central nervous system prophylaxis for Group III patients with cranial parameningeal sarcoma increased S rate to 67% from 45% in IRS‐I (P < 0.001). Patients in Group IV received the same regimens as Group III; the CR rate was 53%, 38% remained in CR and S rate was 27% with and 26% without Adr (P = 0.90). At 5 years, S rate for IRS‐II, including EA and all pelvic tumors, was 63%: an 8% increase over IRS‐I (P < 0.001). Outcomes by primary site were as good as, or better than, the IRS‐I experience. Conclusions. Combining all Groups and treatments in IRS‐II, the major improvement in S rate at 5 years between studies was in nonmetastatic patients (71% for IRS‐II versus 63% for IRS‐I, P = 0.01).

Purpose. To enumerate lessons from studying 4292 patients with rhabdomyosarcoma (RMS) in the Intergroup Rhabdomyosarcoma Study Group (IRSG, 1972-1997).Patients. Untreated patients < 21 years of age at diagnosis received systemic chemotherapy, with or without irradiation (XRT) and/or surgical removal of the tumor.Methods. Pathologic materials and treatment were reviewed to ascertain compliance and to confirm response and relapse status.Results. Survival at 5 years increased from 55 to 71% over the period. Important lessons include the fact that extent of disease at diagnosis affects prognosis. Re-excising an incompletely removed tumor is worthwhile if acceptable form and function can be preserved. The eye, vagina, and bladder can usually be saved. XRT is not necessary for children with localized, completely excised embryonal RMS. Hyperfractionated XRT has thus far not produced superior local control rates compared with conventional, once-daily XRT. Patients with non-metastatic cranial parameningeal sarcoma can usually be cured with localized XRT and systemic chemotherapy, without whole-brain XRT and intrathecal drugs. Adding doxorubicin, cisplatin, etoposide, and ifosfamide has not significantly improved survival of patients with gross residual or metastatic disease beyond that achieved with VAC (vincristine, actinomycin D, cyclophosphamide) and XRT. Most patients with alveolar RMS have a tumor-specific translocation. Mature rhabdomyoblasts after treatment of patients with bladder rhabdomyosarcoma are not necessarily malignant, provided that the tumor has shrunk and malignant cells have disappeared.Discussion. Current IRSG-V protocols, summarized herein, incorporate recommendations for risk-based management. Two new agents, topotecan and irinotecan, are under investigation for patients who have an intermediate or high risk of recurrence.

Better understanding of biologic differences and new, active agents are needed to improve outcome of patients with unfavorable features at presentation.