This study addressed two major questions regarding therapeutic use of Adriamycin ([Adr] Adria Laboratories, Columbus, OH) in adult soft tissue sarcomas: the influence of dosing schedule and the value of adding imidazole carboxamide (DTIC) to Adr. Patients with objectively measurable metastatic soft tissue sarcomas were randomized to Adr 70 mg/m2 intravenously (IV) day 1 and every 3 weeks (94 patients); Adr 20 mg/m2 IV day 1, 2, and 3, and 15 mg/m2 IV day 8 and weekly thereafter (89 patients); and Adr 60 mg/m2 IV day 1 and DTIC 250 mg/m2 days 1 to 5, repeated every 3 weeks (92 patients). The regimens using Adr as a single agent resulted in an equivalent response frequency (18% and 16%) and survival (median, 8.0 and 8.4 months). DTIC significantly increased (P less than .02) the overall response frequency of Adr to 30%. However, DTIC did not influence survival (median, 8.0 months) or increase the number of complete responses. The toxicities of the two single-agent regimens differed: Adr weekly resulted in more stomatitis (P = .09) and less hematologic toxicity (P less than .05). DTIC resulted in substantially increased toxicity, primarily gastrointestinal (P less than .002); overall, 98% of patients receiving Adr-DTIC experienced moderate or worse toxicity. To decrease the potential for error in interpretation of treatment results, histopathological confirmation of diagnosis was undertaken by a panel of reference pathologists; pathology slides were submitted on 97% of entered patients. The on-study clinical diagnosis was affirmed in 199 of 316 patients (63%) with a final review. In 23% of patients, the panel agreed with the diagnosis of soft tissue sarcoma, but not with the type. In 14%, the panel concluded that a diagnosis of mesenchymal malignancy could not be affirmed. Final treatment results were based on the 275 pathologically confirmed, eligible patients. The most common histological subtype entered was leiomyosarcoma (99 patients). The response to Adr-DTIC of this subtype was higher (44%) than that of any other subtype. However, this difference alone was not responsible for the overall superiority of the combination. This confirmed that the combination of DTIC plus Adr adds to the response rate of Adr alone in soft tissue sarcomas. Whether the increased response frequency, without an impact on survival, is worth the significantly greater toxicity remains a subjective judgement that must be made within the context of the individual patient.

Malignant schwannomas with rhabdomyoblastic differentiation have been termed malignant “Triton” tumors (MTT). To define the natural history of MTT, we have analyzed our experience (9 cases, the largest series reported) in combination with the 27 previously described in the literature (total 36 cases). This study was initiated due to the unusual presentation of MTT as a polypoid esophageal mass. Rhabdomyoblastic differentiation in these tumors was confirmed using myoglobin immunohistochemistry. Two groups of patients were identified: those with Von Recklinghausen's Neurofibromatosis (Group I, VRN cases); and those without (Group II, sporadic, non‐VRN cases). Group I patients accounted for over 70% of cases and displayed a marked male predominance, young age, and common head and neck presentation. By contrast, Group II patients were older, had a female predominance, and tumors frequently located on the trunk. Both groups fared equally poorly: local recurrence was common and the 5‐year survival rate for all cases was 12%. Our data support the view that the natural history of MTT, whether in VRN patients or not, is much more aggressive than sporadic malignant schwannoma and similar to VRN sarcomas in general. This poor outlook could not be attributed to site; rather, it appeared to reflect the high frequency of Grade III histology in this disease.

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