Faculty Bibliography

PIP: Antiestrogens, e.g., nafoxidine, tamoxifen, and clomiphene, have been reported to induce objective clinical remissions in patients with breast cancer. Review of data indicates activity of these agents in renal and prostate cancer. In a trial of nafoxidine in 20 patients with adenocarcinoma of the kidney, 2 complete and 1 partial regressions were observed. Stabilization of the disease for 3 months was noted in 5 patients. In another trial, 2 of 4 patients with renal cancer responded to tamoxifen. Similar experiences have been recorded in endometrial cancer with clomiphene. In patients with prostatic cancer, responses have been reported in 1 of 2 patients receiving nafoxidine and in 2 of 4 receiving tamoxifen. These preliminary clinical data should encourage trial of antiestrogens in malignancies other than breast cancer. Estrogen receptor studies may help identify patients most likely to benefit. These agents have a relative lack of toxicity.

A tentative evaluation is proposed for the clinical status of 15 early and investigational drugs in human solid tumors.

An initial clinical phase I trial of isophosphamide has been carried out at dose levels of 200-10,000 mg/m2 of body surface area using a single-dose, every-3-week schedule. Significant toxicity was not seen at isophosphamide dose levels less than 2900 mg/m2. At higher doses, nausea and vomiting was nearly universal. Hematologic toxicity manifested by leukopenia occurred in 12 of 20 patients treated with doses of 3800-7000 mg/m2. Thrombocytopenia to 100,000 platelets/mm3 was not seen in any patient. Urinary bladder toxicity manifested by hemorrhagic cystitis was seen in 15 of 23 patients treated with doses of 3800-10,000 mg/m2. Hemorrhagic cystitis could be completely prevented by bladder irrigation with N-acetyl-L-cysteine (1% solution, 2000 ml/day). With careful attention to hydration, renal toxicity was largely prevented with blood urea nitrogen elevations to 30 mg/dl in only two of 14 patients receiving isophosphamide doses of 5000-7000 mg/m2. Another side effect was central nervous system toxicity in seven of 17 patients at doses of 5000-10,000 mg/m2. For phase II trials a dose of 5000 mg/m2 is recommended, with careful attention to the state of hydration in the patient and with the knowledge that bladder irrigation may be necessary for the prevention and/or amelioration of bladder toxicity.

Abdominal irradiation may produce eosinophilia. The relationship between radiation-related eosinophilia (RRE), reactivity to 2-4 dinitrochlorobenzene (DNCB), lymphocyte count, and prognosis was evaluated in 98 patients irradiated for tumors below the diaphragm. Forty-two per cent manifested RRE and 62% reacted to DNCB. Fifteen of 19 (79%) reactors who had RRE were disease-free at 6 months. Fourteen of 22 (64%) nonreactors who had RRE and 26 of 42 (62%) DNCB reactors without RRE were controlled. Fourteen of 15 (93%) nonreactors without RRE had disease at 6 months. Those who had RRE had double the median survival of those who did not.

Four men with metastatic carcinoma (two bronchus, one stomach, one primary unknown) and ectopic placental protein production (one chorionic gonadotropin (hCG and its alpha subunit; one placental lactogen (hPL); one hCG alone; one hCG and hPL) were studied with serial retrospective measurements of the ectopic protein concentrations in serum, correlated with objective assessment of clinical status. The biochemical marker and clinical response were documented during treatment with a variety of agents and during periods without therapy. Of nine assessable periods, seven showed concordance of biochemical marker and clinical responses.

The spread pattern was studied in 48 autopsied cases of irradiated, apparently localized lung cancer. Disease was found in the upper abdomen in 52%, in the brain in 8.7%; in the bones in 20.8%; and confined to the thoracic cavity in 27%. Radical irradiation controlled 38% locally. The pattern of metastasis in these irradiated lung tumors did not seem to differ from that of unirradiated lung cancers reported elsewhere.