No abstract

Switching from a thymidine nucleoside analogue to either tenofovir DF or abacavir leads to significant improvement in limb fat mass over 48 weeks. Tenofovir DF may have modest advantages over abacavir for changes in lipids. Peripheral lipoatrophy, when clinically apparent, resolves slowly following treatment switching.

Daunomycin is a new antibiotic in the anthracycline group obtained from Streptomyces peucetius. It consists of a pigmented aglycone (daunomycinone) in glycoside linkage with an amino sugar (daunosamine). Differences in the biological effects of daunomycin, which reacts with DNA, and actinomycin D which complexes with DNA in a different manner to inhibit RNA production, are discussed. The toxic effects of daunomycin are a severe local reaction if the drug extravasates, bone marrow depression resulting in leucopenia, anemia, thrombocytopenia and bleeding, fever, oral ulcers and alopecia. In patients receiving maintenance doses of daunomycin the development of tachypnea, tachycardia pulmonary insufficiency, heart failure and hypotension possibly is associated with daunomycin but the evidence is unclear. Sixty per cent of children with leukemia obtained brief complete or partial hematological remissions from a single course of daunomycin. The remission could be prolonged by maintenance therapy. Daunomycin is temporarily effective in some cases of neuroblastoma, reticulum cell sarcoma and rhabdomyosarcoma.

In an attempt to shrink primary osteogenic sarcoma and allow complete surgical removal of the primary tumor, without amputating the involved limb, intensive preoperative chemotherapy with high dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) and adriamycin (ADR) was initiated in 20 patients with biopsy-proven primary osteogenic sarcoma of the distal femur (15 patients) and proximal tibia (five patients). Following intensive chemotherapy, en bloc resection of the primary tumor with prosthetic replacement of the involved bone was planned. After surgery, adjuvant chemotherapy, consisting of HDMTX with CFR, ADR, and high dose cyclophosphamide was given sequentially for 1 year. Of 20 patients with primary osteogenic sarcoma (two with evidence of pulmonary metastases), 18 had primary tumors that could be clinically measured. Of these 18, 17 demonstrated a decrease in the size of primary tumor prior to surgery, while on chemotherapy. To date, 12 of these patients with osteogenic sarcoma of the distal femur have had total femur and knee joint replacement, and three patients with osteogenic sarcoma of the proximal tibia have had total knee replacement. In all 15 patients, surgical margins were grossly and microscopically free of tumor. There has been no evidence of soft tissue recurrence in any of the 15 patients who have undergone surgery for from 2 to 15 months postoperatively. These preliminary results indicate that with the use of aggressive chemotherapy, it is possible to demonstrate objective tumor regression in primary osteogenic sarcoma, allowing the surgeon to perform en bloc resection of tumor and prosthetic replacement of the involved bone. Although the limb is preserved, it is important to stress that extensive surgery yielding tumor-free margins is performed. The ultimate evaluation of this approach to the treatment of primary osteogenic sarcoma awaits longer observation, to determine limb function and the continued disease-free status, once adjuvant chemotherapy is discontinued.

Since May 1970, 67 consecutive patients with primary (nonmetastatic) Ewing's sarcoma were treated with adjuvant chemotherapy (CT) in addition to radiation therapy (RT) or surgery for the primary tumor. The first 19 patients were treated with four-drug sequential CT (T-2). The second protocol was a seven-drug induction combination CT (T-6) followed by T-2 maintenance CT; in both protocols CT was continued for 18 months. The current protocol (T-9) consists of combination CT given continuously for a period of 9 months. Of the entire group of 67 patients, 47 (70%) had axial and proximal lesions (pelvis, spine, rib, humerus, and femur) and 20 (30%) had distal lesions (forearm, leg, and foot); 53/67 (79%) are surviving free of disease 12--118 months (median 41 months) from the start of treatment. Fifteen of 23 (65%) patients with axial lesions, 19/24 (79%) patients with proximal lesions, and 19/20 (95%) patients with distal lesions are free of disease. Disease-free survivors include 28/39 (72%) male patients and 25/28 (89%) female patients. Thirty-four patients had RT, and 33 had surgery or surgery and RT, in addition to chemotherapy, for local treatment. The disease-free survival rate was 76% in the RT group and 82% in the surgery group; failure in the RT group was attributable to local recurrence in 7/34 (21%) patients. Recent experience with T-9 CT has demonstrated that CT given prior to RT or surgery can cause a great reduction in the size of the primary tumor while allowing the pathologically-eroded bone to heal prior to the initiation of RT; this also allows the high-risk patient with an axial primary (pelvis or spine) to tolerate the aggressive CT needed to prevent distant metastases. In addition to dramatically increasing survival in patients with Ewing's sarcoma, combination CT has helped achieve permanent local control. The superior survival rates for all sites of primary tumor are attributable to the early use of aggressive combination CT.

During therapeutic trials with E. coli L‐asparaginase in 131 children and 143 adults with neoplastic disease the following signs of toxicity have been observed: fever, nausea and vomiting, weight loss, somnolence, lethargy, confusion, hypolipidemia, hyperlipidemia, hypoproteinemia, abnormal liver function tests, fatty metamorphosis of the liver, pancreatitis (in rare instances), azotemia, granulocytopenia, lymphopenia, thrombocytopenia, and hypersensitivity reactions. While these effects have been moderately severe and reversible in most instances, some patients have shown dangerous degrees of toxicity. This has been the case most frequently in adult patients receiving a dose of 5000 IU/kg/day.

Adjuvant chemotherapy was added to local radiation therapy for patients with Ewing's sarcoma to treat widespread microfoci of disease presumed to be present at the time of diagnosis. Since June 1970, 12 children have been treated with radiation therapy and sequential adjuvant chemotherapy: dactinomycin, adriamycin, vincristine, and cyclophosphamide, continued for 2 years. Two children developed reversible congestive heart failure after cumulative adriamycin doses of 905 mg/m2 in one patient and 720 mg/m2 in another patient who had mediastinal irradiation. Adriamycin is now generally limited to cumulative doses of 720 mg/m2 but is further limited to 500 mg/m2 in children who receive mediastinal or pulmonary irradiation. Of 12 children entered into this study and followed for from 10 to 37 months, all continue in disease‐free remission without evidence of recurrent tumor, metastatic tumor, or central nervous system disease.

One hundred thirty‐one children between 1 and 15 years of age have been treated. Ninety‐five children had acute lymphoblastic leukemia (ALL); 13 had other types of leukemia; 8 had lymphoma; and 15 had other solid tumors. The dosage ranged from 10 to 5,000 IU/kg daily. Treatment schedules included maintenance after remission and no maintenance. Nine patients in bone marrow remission with other chemotherapy prior to treatment with A‐ase received a 28‐day course. Six patients received the enzyme intrathecally for meningeal leukemia. Of the 73 adequately treated (over 14 days) ALL patients, the overall remission rate was 62%; the median duration of remission was 60 days with a range of 15 to 248 days. The duration of remission appeared to be independent of dose. Six nonlymphoblastic leukemias demonstrated transient fall in WBC and decreased organ size but no bone marrow remission. One of 4 with Hodgkin's disease demonstrated decrease in size of nodes, liver, and spleen. None of the solid tumors responded. The usual side effects of conventional chemotherapeutic agents, mucous membrane ulcerations, alopecia, and diarrhea were not seen. Side effects included reversible abnormal biochemical liver function tests, fever, and anaphylaxis.