amphotericin-b and Sarcoma

Histoplasmosis is an endemic fungus in several regions of the United States. The diagnosis and treatment of this infection can be challenging in pediatric oncology patients. We present 5 patients diagnosed with histoplasmosis while receiving treatment at a midsize pediatric oncology center in Iowa. Two cases occurred in patients with acute lymphoblastic leukemia and 3 cases in patients with solid tumors. All patients were treated with antifungal therapy and demonstrated excellent clinical response. Histoplasmosis should be considered as a potential cause of nonspecific febrile illness, pulmonary masses, and bone marrow suppression in immunocompromised patients in endemic regions. Prompt and accurate diagnosis can facilitate timely antifungal therapy and avoidance of prolonged hospital stays, invasive testing, unnecessary antibiotics, and unwarranted anticancer therapies.

Topics: Abdominal Neoplasms; Adolescent; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Burkitt Lymphoma; Child; Child, Preschool; Combined Modality Therapy; Desmoplastic Small Round Cell Tumor; Diagnosis, Differential; Early Diagnosis; Endemic Diseases; Febrile Neutropenia; Histoplasmosis; Humans; Immunocompromised Host; Infant; Iowa; Itraconazole; Lung; Lung Neoplasms; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sarcoma

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

Amphotericin B enhances the cytotoxicity of certain antineoplastic agents in vitro and in vivo. A phase II study was designed to evaluate whether this effect can be produced in the treatment of metastatic soft-tissue sarcomas (STS). The program AIDAB consisted of ADM 50 mg/m2 i.v. bolus at day 1; ifosfamide (IFX) 1.5 g/m2 in 1 hour i.v. infusion/day x 3 days; mesna 300 mg/m2 i.v. bolus before and 4 and 8 hours after IFX; dacarbazine (DTIC) 400 mg/m2 i.v. in 6 hours infusion/day x 3 days; and amphotericin B 25 mg/m2 i.v. in 6 hours infusion/day x 3 days; repeated every 4 weeks. There were 25 patients evaluable for response and toxicity, 22 with no previous chemotherapy. The median age was 44, (range: 16-64); 14 males, 11 females with a Karnofsky range of 40 to 90%. The response rate was 48% (4% complete response and 44% partial response). The median duration of response was 6.6 months. Of these 25 patients, 17 (68%) have died; the median survival was 12 months (range: 3-51 months). A total of 175 cycles were given to the 25 patients, with a mean of 7 cycles per patient. Toxicities encountered were leukopenia and/or thrombocytopenia, grade IV (WHO), in 9 patients (36%); fever and chills during amphotericin B infusion in 40%; vomiting, grade III (WHO), in 56%; mild mucositis in 12%, and a symptomatic decrease in cardiac ejection fraction in one patient. There was one toxic death due to severe thrombocytopenia. We can conclude that AIDAB is effective in the treatment of metastatic soft-tissue sarcoma. The addition of amphotericin B did not improve the response rate or survival above what is expected from chemotherapy alone.

Topics: Adolescent; Adult; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Dacarbazine; Doxorubicin; Female; Humans; Ifosfamide; Male; Middle Aged; Pilot Projects; Remission Induction; Sarcoma; Soft Tissue Neoplasms; Survival Analysis

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

The distribution of amphotericin B in lung tissue was studied in 18 patients with primary or secondary lung cancer who underwent thoracotomy and pulmonary resection. At different times before surgery the patients were treated with liposomal amphotericin B 1.5 mg/kg by i.v. infusion over 1h. Blood and lung tissue samples were collected during surgery (one subject for each collecting time) and assayed for amphotericin B levels by HPLC. Due to surgical requirements, it was possible to obtain data from the 10th to the 25th h after the end of infusion. Plasma amphotericin B concentrations progressively decreased from 3.4 microg/ml at the 10th h to 1 microg/ml at the 25th h after the end of intravenous infusion. In lung tissue samples the lowest amphotericin B concentration (about 1 microg/g) was observed at the 10th h, then a progressive increase was observed with the highest value (2.5 microg/g) determined at the 25th h.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Chromatography, High Pressure Liquid; Female; Humans; Infusions, Intravenous; Liposomes; Lung; Lung Neoplasms; Male; Middle Aged; Sarcoma; Thoracotomy

Chronic systemic (hepatosplenic) candidiasis (CSC) is a syndrome of invasive candidiasis characterized by fever without localizing signs or symptoms. It occurs predominantly in patients with acute leukemia, after prolonged severe neutropenia. We report a young woman who underwent extensive chemotherapy for granulocytic sarcoma of the ovary; CSC then developed in this patient. She was successfully treated with fluconazole and liposomal amphotericin B. Clinical presentation, diagnostic problems, and the current successful treatment with fluconazole and liposomal amphotericin B are discussed.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Candidiasis; Chronic Disease; Female; Fluconazole; Humans; Liver Diseases; Opportunistic Infections; Ovarian Neoplasms; Sarcoma; Splenic Diseases; Tomography, X-Ray Computed

Topics: Amphotericin B; Candidiasis; Child; Female; Humans; Liver Diseases; Liver Neoplasms; Sarcoma; Therapeutic Irrigation

Nineteen patients resistant to an adriamycin-containing regimen were treated with 4 days of amphotericin B and the same adriamycin-containing chemotherapy regimen that had been given without amphotericin B. Of the 14 evaluable patients (11 with breast carcinoma and three with sarcoma), one patient with breast carcinoma achieved a partial remission and a second patient with breast carcinoma remained stable. All other patients developed progressive disease. Both hematologic and nonhematologic toxicity were significantly increased when amphotericin B was added to chemotherapy.

Topics: Adult; Aged; Amphotericin B; Antineoplastic Agents; Breast Neoplasms; Cyclophosphamide; Dacarbazine; Doxorubicin; Drug Therapy, Combination; Female; Fluorouracil; Humans; Middle Aged; Neoplasm Metastasis; Sarcoma; Vincristine

Three lines of Leishmania have been grown successfully in tissue culture. L. mexicana mexicana, L.tropica major and L. donovani develop readily as amastigotes in dog sarcoma cells, and in a hamster peritoneal exudate cell line. The procedures used for cultivating both host cells and parasites are described, as are the methods employed for studying the senitivity of the parasites and hosts to drugs. It is concluded that the use of a tissue culture system is a valid way of determining the baseline sensitivity of a Leishmania to chemotherapy and the limitations of the technique are discussed. Illustrative data are presented of the response of two Leishmania species to amphotericin B and to a quinine analogue. L. mexicana mexicana is highly sensitive to amphotericin B and the response is shown to be consistent in duplicate experiments. L. mexicana mexicana and L. donovani are shown to have a different innate sensitivity to the quinine analogue.

Topics: Amphotericin B; Animals; Antiprotozoal Agents; Ascitic Fluid; Cell Line; Cells, Cultured; Cricetinae; Dogs; Drug Evaluation, Preclinical; Humans; Leishmania; Methods; Quinine; Sarcoma

Topics: Amphotericin B; Animals; Cell Line; Cells, Cultured; Dogs; Drug Resistance, Microbial; Humans; Leishmania; Methods; Mice; Sarcoma; Trypanosoma cruzi

Topics: Adrenocorticotropic Hormone; Amphotericin B; Blood Transfusion; Bone Marrow Examination; Drug Therapy; England; Geriatrics; Histoplasmosis; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Neoplasms; Pathology; Prednisolone; Sarcoma; Toxicology

Topics: Amphotericin B; Anti-Bacterial Agents; Antineoplastic Agents; Candidiasis; Drug Therapy; Esophagoscopy; Esophagus; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Multiple Myeloma; Neoplasms; Sarcoma