melphalan and Sarcoma--Kaposi

Although the classic form of Kaposi sarcoma is considered indolent and benign, at times its evolution is more severe, with an acute onset and debilitating complications necessitating aggressive treatment and even amputation.. To evaluate the efficacy of hyperthermic isolated limb perfusion (ILP) with tumor necrosis factor alpha and melphalan as a limb-sparing modality for extensive regional Kaposi sarcoma.. University hospital and national referral center.. Five patients, aged 60 to 82 years, with extensive, symptomatic, classic Kaposi sarcoma of the lower limb were operated on. All were candidates for amputation owing to debilitating symptoms.. Patients underwent ILP through the iliac (n = 2), femoral (n = 2), and popliteal (n = 1) vessels. Tumor necrosis factor alpha, 4 mg, and melphalan, 1.5 mg/kg body weight, were perfused for an overall time of 90 minutes. The limb was heated to 40 degrees C. Clinical and pathological responses were recorded for all patients after 6 to 8 weeks.. The overall response rate was 100%: 1 of 5 patients had complete response and 4 of 5 had partial response. Two patients had progression of disease 2 months after ILP but one of them was asymptomatic and did not require any further treatment. The second patient underwent amputation. Thus, limb preservation was achieved in 80% (4 of 5 patients). Median follow-up was 24 months. There were no deaths associated with treatment or major system complications. Local complications were all reversible.. These findings suggest that hyperthermic ILP with tumor necrosis factor alpha and melphalan can be considered an effective palliative and limb-sparing treatment modality for extensive Kaposi sarcoma.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Follow-Up Studies; Humans; Leg; Male; Melphalan; Middle Aged; Perfusion; Sarcoma, Kaposi; Tumor Necrosis Factor-alpha

Topics: Adolescent; Adult; Child; Clinical Trials as Topic; Dysgerminoma; Female; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Melphalan; Middle Aged; Neoplasms; Osteosarcoma; Sarcoma, Kaposi

The aim of this study was to investigate the response rates of different extremity soft-tissue sarcoma subtypes (eSTS) after isolated limb perfusion (ILP), based on an international multi-centre study.. The retrospective cohort comprised eSTS patients from 17 specialised ILP centres that underwent melphalan-based ILP, with or without recombinant human tumour necrosis factor (rhTNFα) (TM-ILP and M-ILP, respectively). Response was measured on imaging (magnetic resonance imaging) and/or clinical response, for which M-ILPs were excluded.. A total of 1109 eSTS patients were included. The three most common histological subtypes were undifferentiated pleomorphic sarcoma (17%, n = 184), synovial sarcoma (16%, n = 175) and myxofibrosarcoma (8%, n = 87). rhTNFα was used in 93% (TM-ILP) and resulted in a significantly better overall response rate (ORR, p = 0.031) and complete responses (CR, p < 0.001) in comparison to M-ILP, without significant differences among histological subgroups. The ORR of TM-ILP was 68%, including 17% CR. Also, 80% showed progressive disease. Significantly higher response rates were shown for Kaposi sarcoma (KS) with 42% CR and 96% ORR (both p < 0.001), and significantly higher CR rates for angiosarcoma (AS, 45%, p < 0.001) and clear cell sarcoma (CCS, 31%, p = 0.049). ILP was followed by resection ≤ 6 months in 80% of the patients. The overall limb salvage rate was 88%, without significant differences among histological subgroups, but was significantly higher for ILP responders compared to non-responders (93% versus 76%, p < 0.001).. ILP resulted in high response and LRS among all eSTS subtypes, however, with significant differences between subtypes with most promising results for KS, AS and CCS.

Topics: Adult; Antineoplastic Agents, Alkylating; Chemotherapy, Cancer, Regional Perfusion; Extremities; Humans; Melphalan; Perfusion; Retrospective Studies; Sarcoma; Sarcoma, Kaposi; Soft Tissue Neoplasms; Tumor Necrosis Factor-alpha

Kaposi sarcoma (KS) is a rare soft tissue sarcoma. In case of locally advanced disease, mutilating surgery such as amputations or major reconstructive procedures are sometimes inevitable. The aim of this study was to evaluate the effectiveness of isolated limb perfusion (ILP) in patients with locally advanced KS of the extremities.. All patients who underwent ILP for KS between 1996 and 2018 at Erasmus MC, Rotterdam were identified. Clinical data was obtained from either a prospectively maintained database or retrospective assessment of patient files.. A total of 14 primary ILP's were performed in 11 patients. Median follow-up from primary ILP was 30 months (range, 5-98). The overall response rate of primary ILP was 100%, with a complete response (CR) rate of 50%. Only minimal local toxicity (Wieberdink I-III) was observed. Local progressive disease occurred after eight primary ILP's (57%) with a median local progression free survival (PFS) of 18 months (95% confidence interval [CI]: 7.0-28.9). Subsequently, four (46%) patients received a total of 5 recurrent ILP's. After the recurrent ILP on the same leg, the overall response rate was 75% and a CR-rate of 50%. One patient needed amputation post-operatively resulting in a limb salvage rate of 91%. One (9%) patient developed metastases four months after ILP.. ILP is a highly effective treatment modality with very limited morbidity rates for patients with locally advanced KS of the extremity. ILP should be considered as a treatment modality for locally advanced KS of the extremities.

Topics: Aged; Amputation, Surgical; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Cancer, Regional Perfusion; Disease Progression; Extremities; Female; Follow-Up Studies; Humans; Male; Melphalan; Middle Aged; Progression-Free Survival; Retrospective Studies; Sarcoma, Kaposi; Soft Tissue Neoplasms; Survival Rate; Treatment Outcome; Tumor Necrosis Factor-alpha

Isolated limb infusion (ILI) is an attractive, less complex alternative to isolated limb perfusion (ILP). It has a lower morbidity in treating localized recurrences and in transit metastases of the limb for tumours such as melanoma, Merkel cell tumour and Kaposi's sarcoma, allowing administration of high concentrations of cytotoxic agent to the affected limb under hypoxic conditions. Melphalan is the preferred cytotoxic agent for the treatment of melanoma by ILP or ILI. We report pharmacokinetic data from 12 patients treated by ILI for tumours of the limb in Brisbane. The kinetics of drug distribution in the limb was calculated using a two-compartment vascular model, where both tissue and infusate act as well-stirred compartments. Analysis of melphalan concentrations in the perfusate during ILI showed good agreement between the values measured and the concentrations predicted by the model. Recirculation and wash-out flow rates, tissue concentrations and the permeability surface area product (PS) were calculated. Correlations between the PS value and the drug concentrations in the perfusate and tissue were supported by the results. These data contribute to a better understanding of the distribution of melphalan during ILI in the limb, and offer the opportunity to optimize the drug regimen for patients undergoing ILI.

Topics: Aged; Antineoplastic Agents, Alkylating; Carcinoma, Merkel Cell; Dose-Response Relationship, Drug; Female; Humans; Infusion Pumps; Leg; Male; Melanoma; Melphalan; Middle Aged; Models, Biological; Neoplasm Recurrence, Local; Sarcoma, Kaposi; Skin Neoplasms; Time Factors

Hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor alpha (TNFalpha) is effective for advanced melanoma and sarcoma of the limbs. Ten patients undergoing HILP with TNFalpha were evaluated by neurological examinations, nerve conduction studies (NCS), sympathetic skin responses (SSR) and conventional and quantitative electromyography (EMG), performed before, 7 days and 6 weeks following HILP. Seven patients showed minimal clinical signs of peripheral nerve damage following HILP; in two the injury was evident electrophysiologically: 7 days following HILP five patients had paresthesias and/or hypoesthesia, one had a mild foot drop and one had autonomic disturbances in the affected limb. SSR was low in two patients in the affected limb, sensory nerve action potentials were not elicited in one, with normal motor NCS and EMG. At 6 weeks, four patients continued to have mild paresthesias and one had dysautonomia of the perfused limb. Sensory responses and SSR did not change, motor abnormalities were not found. These findings show that HILP with TNFalpha induces a mild, mainly sensory neuropathy in perfused limbs, not disturbing functionality and improving over time.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Arm; Autonomic Nervous System Diseases; Chemotherapy, Cancer, Regional Perfusion; Combined Modality Therapy; Electromyography; Female; Humans; Hyperthermia, Induced; Immunologic Factors; Leg; Male; Melanoma; Melphalan; Middle Aged; Neural Conduction; Paresthesia; Peripheral Nervous System Diseases; Prognosis; Reflex, Abnormal; Sarcoma, Kaposi; Soft Tissue Neoplasms; Tumor Necrosis Factor-alpha

We report a case of Kaposi's sarcoma in a patient who underwent autologous bone marrow transplantation (ABMT) for multiple myeloma. Four months after ABMT he presented with numerous asymptomatic, dark blue and purplish macules and nodules on the trunk and lower extremities. Biopsy revealed the typical histologic pattern of Kaposi's sarcoma. The patient died due to disseminated Kaposi's sarcoma while in complete remission of his hematologic malignancy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Transplantation; Combined Modality Therapy; Cyclophosphamide; Etoposide; Fatal Outcome; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Stem Cells; Humans; Immunocompromised Host; Immunologic Factors; Interferon alpha-2; Interferon-alpha; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Recombinant Proteins; Sarcoma, Kaposi; Skin Neoplasms; Transplantation, Autologous

We report on a patient with primary cutaneous malignant melanoma, with numerous intransit metastases involving the left lower extremity. The clinical presentation was striking in that the intransit metastatic lesions of the skin had morphologic characteristics of Kaposi's sarcoma. Her disease was complicated by marked lower limb edema. Cutaneous ulceration did not develop despite the extensive tumor burden. Treatment with regional limb perfusion resulted in marked reduction of the edema and shrinkage of the tumor mass. In addition to presenting this case report and response to therapy, we would like to suggest the term "chronic melanoma of the extremity" (CME) as a descriptive term for this unusual variant of malignant melanoma.

Topics: Aged; Chemotherapy, Cancer, Regional Perfusion; Female; Humans; Leg; Melanoma; Melphalan; Sarcoma, Kaposi; Skin Neoplasms

A patient with multiple myeloma (MM) who developed Kaposi sarcoma (KS) is described. The KS appeared 18 months after the diagnosis of MM and 1 month after the treatment was changed from cyclophosphamide to melphalan. The treatment with melphalan was discontinued and the spread of the KS was arrested by irradiation and bleomycin. One month after the melphalan was restarted, the KS advanced. The patient died 28 months after the diagnosis of MM and 10 months after KS had developed. The association of KS and MM is discussed and the previously reported cases are reviewed. A possible connection between the treatment with melphalan and the development of KS is proposed.

Topics: Bleomycin; Cyclophosphamide; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Neoplasms, Multiple Primary; Sarcoma, Kaposi

Described is a patient with multiple myeloma who, during long-term treatment with alkylating agents, developed cutaneous Kaposi's sarcoma. Patients with multiple myeloma, unlike those with malignant lymphoma, do not usually develop Kaposi's sarcoma during the natural course of the disease. It is suggested that the immunosuppression resulting from the long-term alkylating agent therapy for multiple myeloma may have prediposed this individual to the development of Kaposi's sarcoma.

Topics: Aged; Alkylating Agents; Humans; Male; Melphalan; Multiple Myeloma; Neoplasms, Multiple Primary; Prednisone; Sarcoma, Kaposi

Topics: Adult; Aged; Arm; Chemotherapy, Cancer, Regional Perfusion; Female; Hemangiosarcoma; Humans; Leg; Male; Melanoma; Melphalan; Middle Aged; Oxygenators; Sarcoma; Sarcoma, Kaposi

Topics: Arm; Burns; Chemotherapy, Cancer, Regional Perfusion; Dactinomycin; Edema; Femoral Neoplasms; Foot Diseases; Hemangiosarcoma; Hemoglobinuria; Hemolysis; Hot Temperature; Humans; Leg; Melanoma; Melphalan; Neoplasm Metastasis; Sarcoma; Sarcoma, Ewing; Sarcoma, Kaposi; Time Factors

Topics: Aorta; Aorta, Abdominal; Bone Neoplasms; Carotid Arteries; Chemotherapy, Cancer, Regional Perfusion; Chondrosarcoma; Dactinomycin; Dogs; Fibrosarcoma; Iliac Artery; Iliac Vein; Leiomyosarcoma; Liposarcoma; Lymphoma, Non-Hodgkin; Melphalan; Mesothelioma; Neoplasms; Neuroblastoma; Osteosarcoma; Rhabdomyosarcoma; Sarcoma; Sarcoma, Kaposi; Subclavian Artery; Vena Cava, Inferior

Topics: Adolescent; Child; Geriatrics; Head and Neck Neoplasms; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mandibular Neoplasms; Maxillary Neoplasms; Melanoma; Melphalan; Multiple Myeloma; Neoplasms; Orbital Neoplasms; Plasmacytoma; Sarcoma; Sarcoma, Kaposi