FDA approved Matulane (procarbazine) for Stage III and IV Hodgkin's DiseaseFDA approved Matulane for advanced Hodgkin's disease in combination therapy

Not reported in label.

Matulane is indicated for use in combination with other anticancer drugs for the treatment of Stage III and IV Hodgkin's disease. It is used as part of the MOPP regimen (nitrogen mustard, vincristine, procarbazine, prednisone).

All dosages are based on the patient's actual weight, but estimated lean body mass (dry weight) is used if the patient is obese or has spurious weight gain due to edema, ascites, or other abnormal fluid retention.

Adults: To minimize nausea and vomiting, single or divided doses of 2 to 4 mg/kg/day for the first week are recommended. Daily dosage should then be maintained at 4 to 6 mg/kg/day until maximum response is obtained or until white blood count falls below 4000/cmm or platelets fall below 100,000/cmm. When maximum response is obtained, the dose may be maintained at 1 to 2 mg/kg/day. Upon evidence of hematologic or other toxicity, the drug should be discontinued until satisfactory recovery. After toxic side effects subside, therapy may be resumed at the physician's discretion at a dosage of 1 to 2 mg/kg/day.

Pediatric Patients: Very close clinical monitoring is mandatory. Dosage should be individualized. A guideline: 50 mg/m2/day for the first week, then 100 mg/m2/day until maximum response or leukopenia/thrombocytopenia occurs. When maximum response is attained, the dose may be maintained at 50 mg/m2/day. Upon evidence of toxicity, discontinue until satisfactory recovery, then resume.

When used in combination with other anticancer drugs, the Matulane dose should be appropriately reduced; in the MOPP regimen, the dose is 100 mg/m2 daily for 14 days.

Trial data not available in label.

To minimize CNS depression and possible potentiation, barbiturates, antihistamines, narcotics, hypotensive agents, or phenothiazines should be used with caution. Ethyl alcohol should not be used due to a possible Antabuse (disulfiram)-like reaction. Because Matulane exhibits some monoamine oxidase inhibitory activity, sympathomimetic drugs, tricyclic antidepressants (e.g., amitriptyline, imipramine), and other drugs and foods with high tyramine content (e.g., wine, yogurt, ripe cheese, bananas) should be avoided. Hemolysis and Heinz-Ehrlich inclusion bodies in erythrocytes may occur.

Pregnancy: Procarbazine hydrochloride can cause fetal harm. There are case reports of malformations in offspring of women exposed during pregnancy. Use during pregnancy only if potential benefit justifies potential risk. Women of childbearing potential should avoid becoming pregnant. Procarbazine is teratogenic in rats at doses 4 to 13 times the maximum recommended human therapeutic dose of 6 mg/kg/day. Nonteratogenic effects: not adequately studied in animals; neurogenic tumors were noted in offspring of rats given intravenous 125 mg/kg on day 22 of gestation.

Carcinogenesis: Carcinogenicity in mice, rats, and monkeys has been reported. Second nonlymphoid malignancies, including lung cancer and acute myelocytic leukemia, have been reported in patients with Hodgkin's disease treated with procarbazine in combination with other chemotherapy and/or radiation. Risk of secondary lung cancer may be multiplied by tobacco use. IARC considers sufficient evidence for human carcinogenicity in intensive regimens including other antineoplastic agents, but inadequate evidence for procarbazine alone.

Mutagenesis: Procarbazine is mutagenic in various bacterial and mammalian test systems.

Impairment of Fertility: Azoospermia and antifertility effects have been reported.

Matulane is a component of the MOPP regimen for Stage III and IV Hodgkin's disease. It is used in combination with other anticancer drugs. The label does not provide comparative efficacy data or guidance on patient selection beyond the indication