amphotericin-b and Bone-Neoplasms

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by Paracoccidioides brasiliensis, which is endemic in many regions of Latin America. We describe the case of a 60-year-old man from a region endemic for PCM who presented with a long history of left hip pain. He had been treated over the past 3 years with immunosuppressive drugs (methotrexate, leflunomide, and adalimumab) for rheumatoid arthritis (RA). A hip radiograph showed lytic bone lesions, and a chest radiograph showed an expansive excavated lesion in the left lung, suggestive of a lung cancer with bone metastases. A left hip joint biopsy was inconclusive, but histological analysis of a surgical lung biopsy specimen was consistent with P. brasiliensis infection. Treatment with intravenous amphotericin B (50 mg/day) and hydrocortisone (25 mg/day) was initiated. However, increasing hip pain resulted in the amputation of the left lower limb, and the analysis of the surgical specimen revealed a diagnosis of bone sarcoma. Postoperatively, the patient developed sepsis and died approximately 1 month later. To our knowledge, this is the first report of PCM in a patient with RA who had been treated with immunosuppressive drugs, in particular TNF-α blocking agents. The atypical presentation (left hip pain alone) emphasizes the importance of considering PCM in the differential diagnosis of patients with pulmonary lesions and osteolytic lesions who live in a region endemic for PCM. This case report also demonstrates that health professionals in these regions must pay close attention to patients receiving immunosuppressive drugs because of the possibility of reactivating quiescent P. brasiliensis lesions.

Topics: Adult; Amphotericin B; Antifungal Agents; Arthritis, Rheumatoid; Bone Neoplasms; Fatal Outcome; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Latin America; Lung; Lung Neoplasms; Male; Middle Aged; Paracoccidioides; Paracoccidioidomycosis; Postoperative Complications; Sarcoma; Sepsis

Ninety-four evaluable patients with metastatic soft tissue and bone sarcomas entered into a prospective randomized trial (SEG 78SAR327) to determine whether amphotericin B (AMB), a membrane-permeabilizing and immunopotentiating agent, could increase either the response rates or the survival of patients treated with a three-drug combination chemotherapy regimen consisting of Adriamycin, cyclophosphamide, and methotrexate (ACM). Pretreatment patient characteristics were similar in each arm. In patients treated with ACM there were 4% complete responses and 34% partial responses, compared with only 5% partial responses on ACM + AMB (P less than 0.05). However, there was no difference in the median time to progression (5.0 months on either arm) or in survival (7.0 months on ACM, and 6.0 months on ACM + AMB). Myelosuppression was the dose-limiting toxicity, and was equal in each treatment arm. The addition of AMB to dactinomycin during maintenance therapy did not result in any complete or partial responses. It is concluded that despite definite biologic activity in experimental tumor models, AMB is not useful clinically in potentiating chemotherapeutic drug activity in patients with metastatic sarcomas, and actually results in a decrease in the frequency of objective responses.

Topics: Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Methotrexate; Middle Aged; Random Allocation; Sarcoma

Amphotericin B (AmB), a polyene antifungal antibiotic, has been shown to potentiate the cytotoxic effect of different chemotherapeutic drugs in vivo and in vitro. The purpose of this study was to determine whether AmB could enhance the carboplatin antitumor activity in a human osteosarcoma xenograft model. Nude mice, bearing s.c. transplanted osteosarcoma xenografts, received i.p. an injection of AmB (5 mg/kg) 6 h prior to carboplatin (20 mg/kg) or each of the drugs separately. The effect of treatment was assessed by analyzing tumor growth delay and T/C ratio. Carboplatin clearly reduced tumor growth when administered alone. However, an unexpected interaction was seen where AmB significantly decreased the antitumor effect of carboplatin. The present results contradict some earlier in vitro studies and indicate the complexity of this interaction in vivo. Hence, it seems that interactive phenomena in one experimental model, and especially with regard to AmB, cannot be universally applied to all experimental situations.

Topics: Amphotericin B; Animals; Antifungal Agents; Antineoplastic Agents; Bone Neoplasms; Carboplatin; Cell Division; Drug Interactions; Female; Humans; Mice; Mice, Inbred BALB C; Osteosarcoma; Transplantation, Heterologous

The results of amphotericin B and cyclophosphamide treatment of 10 cases of chondrosarcoma are discussed. A marked (50-90%) regression of tumors and metastases and complete remission for 3-18 months were observed in 9 cases. Decompression laminectomy resulted in regression of neurologic symptoms in a case of chondrosarcoma disseminated to the spinal column with concomitant constriction of the spinal cord. This effect was obtained during remission following chemotherapy.

Topics: Adult; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Chondrosarcoma; Cyclophosphamide; Drug Evaluation; Drug Synergism; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local

Topics: Amphotericin B; Bone Neoplasms; Child, Preschool; Diphosphonates; Histoplasmosis; Humans; Kidney; Kidney Tubular Necrosis, Acute; Male; Radionuclide Imaging; Technetium; Technetium Tc 99m Medronate