Exercise-induced fragmentation hemolysis: a simple in vivo test to evaluate heart valve hemolysis.

Differentiating heart valve-related fragmentation hemolysis from other causes of hemolysis can occasionally be difficult, especially when findings on transthoracic or transesophageal echocardiography are minimal. We report a case in which the cause of hemolysis remained in doubt after thorough hematologic and cardiologic evaluations. The decision to reoperate on the valve was finally made, based on the result of exercise-induced increase in serum hemoglobin. Hemolytic anemia promptly resolved after reoperation. We believe this to be the first reported use of this in vivo test to support the diagnosis of valve-related hemolytic anemia.

Selection of cancer chemotherapy for a patient by an in vitro assay versus a clinician.

One hundred thirty-three patients with advanced metastatic cancer were randomized to receive single-agent chemotherapy selected by either a medical oncologist or an in vitro capillary cloning system. Thirty-six of the 65 patients (55%) who were randomly assigned to selection of a drug by the clinician actually received a drug; these patients were able to be evaluated for clinical response. Of these 36 patients, one had a partial tumor response (3%). Only 19 of the 68 patients (28%) who were randomly assigned to selection of a drug by the capillary system actually received a drug; these patients were able to be evaluated for clinical response. Of these 19 patients, four (21%) had partial tumor responses. In the assessable patients (36 in the clinician's choice group, 19 in the capillary cloning group), the partial response rate was superior for drug selection by the capillary cloning system (P = .04). For all patients randomly assigned to a group (65 in the clinician's choice group, 68 in the capillary cloning group), the response rate was not significantly different (1.5% and 5.9%, respectively; P = .37). When overall survival rates for patients in the two groups were compared, there was no difference. We conclude that drug sensitivity testing in capillary tubes can improve the response rate for patients with advanced malignancies. This improved response rate, however, does not translate into improved survival times for these patients.

Extraneural metastases from medulloblastoma: long-term survival after sequentially scheduled chemotherapy and radiotherapy.

Extraneural relapse of medulloblastoma is an uncommon event which has typically been associated with a fatal outcome. We present a case of a 2 1/2-year-old male who developed extensive bone marrow and bone metastases 19 months after diagnosis and treatment of a medulloblastoma. This patient was successfully treated with a sequentially scheduled combination of vincristine, cyclophosphamide, and doxorubicin and remained free of disease for more than 5 years from the time of relapse.

Prospective clinical trial of a human tumor cloning system.

A prospective clinical trial was performed to evaluate the usefulness of a human tumor cloning system for selecting single-agent chemotherapy for patients with advanced cancers. Six hundred four single-agent trials were performed in the 470 patients whose tumors were submitted for drug sensitivity testing. Only 246 of these 604 trials (41%) could be directed by the cloning system results because of inadequate tumor growth and other difficulties. In these 246 prospective trials, there was a 60% true positive and an 85% true negative rate for predicting for response or lack of response of an individual patient's tumor to the single agent. There was also a relationship between the percentage of decrease in survival of tumor colony-forming units and the probability of a clinical response of the patient's tumor to the same drug used in vivo. Despite these encouraging findings, work to improve tumor growth and additional prospective clinical trials of the system are needed before the system can be recommended for routine clinical use.

Anaphylactoid reactions associated with bisantrene infusions.

Nine of ninety-three patients receiving Bisantrene on an every three week schedule developed an anaphylactoid reaction with a variety of symptoms. Most reactions occurred in patients who had multiple exposures to Bisantrene. Investigators utilizing Bisantrene in ongoing clinical trials should be aware of this life threatening toxicity.

Phase I clinical investigation of 9,10-anthracenedicarboxaldehyde bis[(4,5-dihydro-1 H-imidazol-2-yl)hydrazone] dihydrochloride (CL216,942).

9,10-Anthracenedicarboxaldehyde bis[(4,5-dihydro-1 H-imidazol-2-yl)hydrazone] dihydrochloride (CL216,942) is a new anthracene bishydrazone derivative that was evaluated in a Phase I clinical trial. The schedule of administration consisted of a single i.v. injection repeated at 4-week intervals. Twenty-eight patients received a total of 61 courses of the drug in a dose range of 20 to 280 mg/sq m. Leukopenia was the dose-limiting toxicity. It was of short duration and reversible. A drug-induced hypotension was noted at higher doses in three patients. The hypotension was not dose limiting, it was reversible, and it could largely be avoided by prolonging the drug infusion time to 1 hr. One patient with unsuspected severe coronary artery disease died of complications of myocardial infarction subsequent to a hypotensive episode. Significant phlebitis was also noted at higher doses of drug. This degree of phlebitis could be lessened by diluting the drug in larger volumes of fluid. Three patients experienced diaphoresis, nausea, palpitations, and chest discomfort at the conclusion of the infusions. None of the patients had electrocardiographic changes. Mild fever, alopecia, and nausea and vomiting were noted occasionally. One patient with a hypernephroma and one patient with hepatocellular carcinoma experienced partial responses of their tumors secondary to the drug. Phase II studies of CL216,942 are planned at a starting dose of 260 mg/sq m as a single dose repeated at 21- to 28-day intervals.