melphalan and Fibromatosis--Aggressive

Isolated limb perfusion (ILP) is an established and effective treatment for advanced melanoma and soft tissue sarcomas of the extremities with a high overall response rate. The aim of this study was to describe our experience of ILP for more rare types of tumours.. Patients with Merkel cell carcinoma (MCC) (n = 4), squamous cell carcinoma (SCC) (n = 2), B-cell lymphoma (n = 1), desmoid tumours (n = 3), pigmented villonodular synovitis (PVNS) (n = 1) and giant cell tumour (n = 1) were treated with ILP and analysed retrospectively.. The four patients with in-transit MCC had three complete responses (CR) and one partial response (PR); the two patients with SCC had one CR and one stable disease (SD); the patients with desmoid tumours had two PR and one SD. A CR was also observed for the patient with a giant cell tumour, but the patient with PVNS had a SD. The patient with cutaneous metastases of B-cell lymphoma showed a CR, however with rapid systemic progression. Local toxicity according to Wieberdink was grade II in 10 patients (83%) and grade III in two patients (17%).. These results show that ILP can be used as a treatment option also for more rare disease entities when other treatments have failed.

Topics: Abdominal Neoplasms; Adenomatous Polyposis Coli; Antineoplastic Agents, Alkylating; Carcinoma, Merkel Cell; Carcinoma, Squamous Cell; Chemotherapy, Cancer, Regional Perfusion; Extremities; Fibromatosis, Aggressive; Giant Cell Tumors; Humans; Hyperthermia, Induced; Lymphoma, B-Cell; Melphalan; Perfusion; Rare Diseases; Synovitis, Pigmented Villonodular; Tumor Necrosis Factor-alpha

In a prior randomized phase II trial comparing hyperthermic isolated limb perfusion (HILP) with four different doses of tumor necrosis factor alpha (TNF-alpha), no dose effect was detected for response, but systemic toxicity was far lower with low-dose TNF-alpha. The objective of the present study was to confirm these data on a larger sample size of locally advanced or recurrent extremity soft tissue sarcomas with low-dose TNF-alpha.. We assessed a prospective database comprising 100 HILP (38-40 degrees C) with melphalan (10 mg/L) and TNF-alpha (1 mg). The remnant tumor was resected 2 months later.. Among 52 recurrences, 18 were in a previously irradiated field. Stages according to the American Joint Committee on Cancer classification were II (19 patients), III (78 patients), and IV (3 patients). The site/size were: 30 patients/57 mm and 70 patients/86 mm for the upper and lower limbs, respectively. Tumor grades (FNCLCC) were 1 (23 patients), 2 (34 patients), and 3 (43 patients). Fifty-one patients had received systemic chemotherapy before HILP. Responses on magnetic resonance imaging were 30% complete, 49% partial, 9% no change, and 12% progression. No mortality or systemic toxicity occurred. Local toxicity (Wieberdink) attained grade 2 (16 patients), 3 (5 patients), and 4 (1 patient). Limbs were able to be saved in 87% patients. Three-year overall survival and the local recurrence rate were 89% and 18%, respectively. Age, sex, tumor size, recurrence, uni- or multifocality, grade, preoperative chemotherapy, and a previously irradiated field were not predictive of response or local toxicity.. We confirm that 1 mg of TNF-alpha is as effective as the standard dose and results in no systemic toxicity.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents, Alkylating; Chemotherapy, Cancer, Regional Perfusion; Drug Therapy, Combination; Extremities; Female; Fibromatosis, Aggressive; Follow-Up Studies; Humans; Hyperthermia, Induced; Male; Melphalan; Middle Aged; Neoplasm Staging; Prognosis; Prospective Studies; Sarcoma; Survival Rate; Tumor Necrosis Factor-alpha; Young Adult

Hyperthermic isolated limb perfusion (ILP) (2 mg, TNF-alpha and 100mg, melphalan) was performed for an irresectable right thigh desmoid tumor with calf extension in a 49-year-old man. The patient had a history of four resections since the age of 19 years. Local ILP toxicity appeared with extensive edema and common peroneal neurologic impairment including paresis that remained severe 10 months later. One of the most troublesome side effects of perfusion is peripheral nerve damage, which has been reported at a rate of between 1 and 48% of perfused patients. ILP is an effective treatment in recurrence situations or where resection threatens loss of function; it, however, requires administration in specialized centers, progress in standardization and close monitoring to avoid locoregional toxicity, the mechanisms of which merit further investigation. Emergency compartmental pressure measurement may indicate fasciotomy, can be of great interest.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Cancer, Regional Perfusion; Electromyography; Fibromatosis, Aggressive; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Melphalan; Middle Aged; Neoplasm Staging; Paralysis; Peroneal Nerve; Risk Assessment; Severity of Illness Index; Soft Tissue Neoplasms; Thigh; Treatment Outcome; Tumor Necrosis Factor-alpha

The management of extensive, recurrent limb desmoid tumors is extremely difficult. The failure of multimodality treatments, such as repeated resections, radiotherapy, systemic chemotherapy, or endocrine manipulations, can end up with multilating surgery or even amputation, similar problems sometimes encountered in soft tissue sarcoma of the limbs. The high rate of limb salvage achieved by isolated limb perfusion (ILP) with tumor necrosis factor (TNF) and melphalan for extensive, high-grade soft tissue sarcoma led us to implement this modality in difficult cases of limb desmoids.. During a 4-year period, 6 patients aged 14 to 52 years were treated. All were significantly symptomatic and candidates for amputation or mutilating surgery. Five had lower and one had upper limb lesions. Two had multifocal disease. At ILP, 3 to 4 mg TNF and 1 to 1.5 mg/kg melphalan were delivered during a 90-minute period. One patient had a double perfusion. All patients underwent definitive resective operation 6 to 8 weeks after perfusion.. No systemic complications were observed, and local complications included reversible skin redness and blisters. Response rate was 83% with 33% (2 of 6) complete response and 50% (3 of 6) partial response. In 1 patient less than 50% regression was observed. Limb salvage rate was 100%; even the patient with stabilization of disease could be locally resected. Local recurrence during a follow-up period of 7 to 55 months (median 45 months) occurred in 2 patients at 8 and 24 months, respectively; the first underwent amputation, whereas for the second a wide excision was possible.. ILP with TNF and melphalan can be used as a limb preservation modality in patients with recurrent desmoids and significant symptoms who would otherwise require multilating surgery to control their neoplasm.

Topics: Adolescent; Adult; Antineoplastic Agents, Alkylating; Drug Therapy, Combination; Extremities; Female; Fibromatosis, Aggressive; Humans; Male; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Perfusion; Recombinant Proteins; Treatment Outcome; Tumor Necrosis Factor-alpha