Cancer Treatment Reports

The long-term survival of patients with high-grade gliomas of the CNS is poor despite the use of radiation therapy and chemotherapy. In an attempt to improve the survival of such patients, we administered adjuvant chemotherapy as high-dose carmustine with autologous bone marrow transplantation. Eighteen patients, 15 with glioblastoma multiforme and three with anaplastic astrocytoma, were treated shortly after completion of standard radiation therapy. One course of carmustine was administered at a total dose of 900-1050 mg/m2 iv over 3 days followed in 3 days by the reinfusion of the previously cryopreserved bone marrow...

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Patients with advanced lymphoma who relapse from intensive first-line combination chemotherapy generally have a very poor prognosis. The use of investigational drugs which lack cross-resistance to agents commonly used for initial therapy represents an important approach to the management of such patients. Based upon our prior experience, we developed a protocol which employed a combination of three new agents. Mitoguazone (600 mg/m2) was administered on Days 1 and 10; etoposide (100-125 mg/m2) was administered on Days 2, 3, and 4; and gallium nitrate (300 mg/m2/day) was administered as a continuous iv infusion over 24 hours on Days 1-7...

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Twenty-four patients with recurrent or metastatic cervical cancer were treated with vindesine (VDS) (2 mg/m2) on 2 subsequent days per week. Twenty patients were evaluable for response. There were six partial responses (30%) and no complete responses. The median remission duration was 6.5 months. The results indicate that VDS is active in the treatment of cervical cancer. Dose-limiting toxic effects were leukopenia and peripheral neuropathy. VDS should be considered in the treatment planning of combination chemotherapy for cervical cancer...

To determine the incidence of cardiovascular autonomic insufficiency (CAI), 43 patients with advanced breast cancer and 20 normal controls were evaluated using electrocardiographic tests (heart rate variation during deep breathing and Valsalva maneuver and upon standing) and clinical tests (blood pressure variation during hand grip tests and upon standing). Nutritional status, tumor mass, Karnofsky performance status (PS) score (0-100), and peripheral reflexes were also determined. Tests for CAI were abnormal in 43 patients (52%), versus seven of 100 in 20 controls (7%, P less than 0...

Fifteen patients with advanced malignancy were treated with escalating doses of recombinant beta ser 17 interferon (IFN). Doses ranging from 0.006 to 500 X 10(6) units/m2 were administered according to a dosage escalation scheme by iv push twice weekly (starting 1 week after an initial dose) for a planned minimum of 5 weeks, to be continued as a function of response. Toxic effects were broad in scope but generally low in grade. They included fever, malaise, leukopenia, proteinuria, nausea/vomiting, diarrhea, and mild elevations of serum transaminases and creatinine...

In this study we show that cytarabine given simultaneously with 5-aza-2'-deoxycytidine (Aza-dC) antagonized Aza-dC activity against L1210 mouse leukemia. This antagonism was seen after a single dose (on Day 3 or Day 5 after tumor implant) and after repeated doses. This observation suggests caution in combining cytarabine with Aza-dC in the treatment of human leukemias.

A serious delayed neurotoxicity marked by encephalopathy and cortical blindness has occurred in patients treated with fludarabine. This toxicity had only been reported in patients receiving high doses (ie, aplasia-inducing). We describe a similar subacute neurological deterioration occurring in two patients, including one who received only low doses of this agent. Neurologic vulnerability to low doses of fludarabine may be multifactorial and at present cannot be predicted. Continued caution in the use of this new antineoplastic agent is appropriate...

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Gallium nitrate is the anhydrate salt of the naturally occurring heavy metal. It has demonstrated antitumor activity in a variety of murine tumor models, including Walker carcinosarcoma 256, fibrosarcoma M-89, leukemia K-1964, adenocarcinoma 755, mammary carcinoma YMC, reticulum cell sarcoma A-RCS, lymphoma P1798, and osteosarcoma 124F. Preclinical studies performed in rats, rabbits, dogs, and monkeys showed the dose-limiting toxicity to be renal. The hepatic, pulmonary, gastrointestinal, hematologic, and integumentary systems were also involved...

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Thirty-six patients with malignant carcinoid tumors were treated with human leukocyte interferon (IFN) im at doses of 3-6 megaunits/day. The origins of the primary tumors were as follows: mid-gut (29 patients); pulmonary (four); rectal (one); ovarian (one); and unknown (one). Nineteen of the 36 patients had previously been treated with cytotoxic agents, streptozocin plus 5-fluorouracil or doxorubicin, but showed progressive disease. With IFN objective tumor responses were seen in 17 of the 36 patients (47%): in 14 of the 29 patients with mid-gut carcinoids (48%) and in three of the four patients with lung carcinoids (75%)...

Gallium nitrate was administered as a 700-mg/m2 iv bolus infusion over 15-30 minutes every 2 weeks to 138 patients with malignant lymphoproliferative diseases. Responses occurred in patients with well-differentiated lymphomas (five responses among eight patients), but the drug produced few responses in any other group of patients. Toxic effects were primarily gastrointestinal and reversible renal abnormalities and anemia. As a single agent, bolus gallium nitrate has little activity in lymphoproliferative diseases...

Protocols used to prepare patients with leukemia for bone marrow transplantation have the potential for cardiac toxicity due to high-dose cyclophosphamide and total-body irradiation. We have reported one regimen, combining cytarabine (5 mg/kg), cyclophosphamide (90 mg/kg), and total-body irradiation (900 cGy), which is relatively effective in the treatment of leukemia. To assess cardiac effects of this treatment regimen, we performed serial echocardiography and radionuclide ventriculography in 28 patients with leukemia (age range, 18-48 years; mean, 31; 21 males) undergoing allogeneic bone marrow transplantation...

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Fourteen patients developed severe central nervous system (CNS) toxicity after receiving an investigational antitumor agent, fludarabine phosphate (FAMP). The CNS toxicity has the distinctive features of delayed onset and progressive clinical course. Visual deficits were the most common presenting symptom and developed eventually in most cases. Deterioration of mental status and progressive encephalopathy were also observed. The development of clinical CNS toxicity appears dose-related; thirteen of 36 patients (36...

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Fourteen patients with metastatic malignant melanoma localized to a lower extremity were treated with combined radiotherapy and intra-arterial infusion therapy with dacarbazine. All lesions that were included in radiation fields regressed completely. Two patients relapsed within radiation fields and six relapsed elsewhere. One patient had a serious intimal lesion caused by the catheter.

Three National Cancer Institute of Canada phase II studies of N-methylformamide (NMF), given in a three times/week oral schedule, closed early because of frequent and occasionally severe toxicity. Eighteen of 41 (44%) cycles of treatment were not completed because of problems with NMF-induced hepatic and gastrointestinal toxicity. Several other reactions occurred, including skin rashes, abdominal pain, and gastritis, which were drug induced. One death occurred on study and was thought to be due in part to NMF toxicity...