Sterility and testicular atrophy related to cyclophosphamide therapy.

We conducted a controlled trial to investigate the long-term effects of treatment with methylprednisolone and chlorambucil in patients with idiopathic membranous nephropathy. We have previously reported that after a mean of 31 months, treated patients did better. We now report the results of a longer follow-up. Eighty-one patients with proteinuria (greater than or equal to 3.5 g per day) and biopsy-proved membranous nephropathy were randomly assigned to receive either supportive therapy alone or a six-month course of corticosteroids alternated with chlorambucil (0.2 mg per kilogram of body weight per day) every other month. Methylprednisolone was first given intravenously in three pulses (1 g per day) and was then given orally (0.4 mg per kilogram per day) for 27 days. The patients were followed for 2 to 11 years (median, 5). Two patients in the control group and one in the treatment group died. At the last follow-up visit, 9 of 39 patients assigned to the control group (23 percent) and 28 of 42 patients assigned to the treatment group (67 percent) did not have the nephrotic syndrome. At five years there were more remissions of the nephrotic syndrome in treated patients than in controls (22 of 30 vs. 10 of 25; P = 0.026). Compared with base-line values, the mean reciprocal of the plasma creatinine level declined significantly in the control group (33 percent; P = 0.0002) but not in the treatment group (6 percent; P not significant). Plasma creatinine increased by 50 percent or more in 19 controls (49 percent) and in 4 treated patients (10 percent). We conclude that a six-month course of methylprednisolone and chlorambucil can bring about sustained remission of the nephrotic syndrome and help to preserve renal function in patients with idiopathic membranous nephropathy.

https://www.nejm.org/doi/pdf/10.1056/NEJM198404123101503?listPDF=true

A Randomized Trial of Methylprednisolone and Chlorambucil in Idiopathic Membranous Nephropathy

Publisher Summary This chapter consolidates and quantitates some deleterious effects of cancer chemotherapeutic agents in humans—namely, their ability to induce chromosomal aberrations, their antifertility effects, their ability to produce congenital malformations under certain conditions, and their carcinogenic potential when used to treat neoplastic and nonneoplastic diseases. It discusses the three classes of antitumor compounds: alkylating agents, antimetabolites, and antitumor antibiotics. These compounds have been extensively studied in vitro and in vivo and they induce chromosomal aberrations; these abnormalities vary according to the agent and the test system used. Combinations of agents or agents plus irradiation also produce cytogenetic damage in human cells. It also provides information on the possible adverse effects of the antimetabolites, antitumor antibiotics, and miscellaneous synthetic agents on spermatogenesis. The current evidence indicates that these effects are related to the dose and duration of chemotherapy, both for single alkylating agents and for combination chemotherapy in which the alkylating agent is one of the components. Anticancer drugs other than the alkylating agents should be more thoroughly studied for possible effects on the fertility in the human female.

Toxicity of antineoplastic agents in man, chromosomal aberrations antifertility effects, congenital malformations, and carcinogenic potential.

Reproductive function was evaluated in 16 men who had been treated with a combination of nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP); a similar combination, with met...

Effect of Drug Treatment for Lymphoma on Male Reproductive Capacity

CYCLICAL COMBINATION CHEMOTHERAPY AND GONADAL FUNCTION: Retrospective Study in Males

This report is concerned with the action of chlorambucil in males. A group of 8 patients with malignant lymphoma were studied. Diagnoses of Hodgkins disease lymphosarcoma and reticulosarcoma had been established by biopsy. Ages were 18 to 38. As the sole medication chlorambucil was given in doses of .1 mg to .4 mg/Kg/day. Hormonal studies were done based on the determination of 17-ketosteroids in the urine and urinary excretion of gonadotropins. Testicular biopsies were performed by open surgery or at autopsy. After treatment 6 patients became azoospermic 1 developed sever oligospermia and 1 showed no change. With total doses up to 400 mg a progressive oligospermia developed from which the patient could recover slowly if the drug was stopped. 4 patients had elevated values of neutral 17-ketosteroids 3 had slightly low values. Gonadotropins were all within normal limits. Micropic studies showed that the germinal like disappears only Sertoli cells remain and peritubular fibrosis develops. The interstitial cells and blood vessels appeared normal. The condition of azoosperma is considered to be permanent.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%28197005%2925%3A5%3C1026%3A%3AAID-CNCR2820250506%3E3.0.CO%3B2-C

Abraham L. Kierszenbaum

Papers

Effect of chlorambucil on spermatogenesis in the human with malignant lymphoma.