High-dose megestrol acetate in the treatment of patients with ovarian cancer who have undergone previous treatment: Eastern Cooperative Oncology Group Study PD884.

High-dose megestrol acetate has been reported to be effective salvage therapy for women with ovarian carcinoma. The Eastern Cooperative Oncology Group performed this phase II study of oral megestrol acetate, 200 mg four times daily until disease progression, in 33 patients either with stage III or IV histologically confirmed ovarian carcinoma or with unresectable tumor in the pelvis with measurable or evaluable disease who progressed after treatment with one prior chemotherapy regimen. Thirty and 31 patients were evaluable for response and toxicity, respectively. No patient had an objective response and none had subjective improvement after a median treatment period of 1.4 months. Nausea or vomiting occurred in most patients, usually grade 1-2. Megestrol acetate is ineffective salvage therapy for patients with inoperable, previously treated ovarian carcinoma.

Smoking, dietary, and breast and cervical cancer screening knowledge and screening practices of employees in an urban medical center.

This paper reports results of a survey of 500 health care workers in a private New York City Hospital that assessed knowledge and behaviors in the areas of smoking and cancer, diet and cancer, and breast and cervical cancer screening. Given the small number of knowledge items, the results indicated good knowledge concerning diet and cancer, smoking and cancer, and mammography and Pap test guidelines. Conformity with American Cancer Society guidelines for Pap testing was comparable to national figures, but with women over 50 as likely to obtain Pap smears as younger women. Conformity with mammography guidelines was excellent, although compliance with breast self-examination recommendations was low (25.4%). Of female employees over age 50, 87.4% had ever had mammography and 77.6% reported yearly mammography. Only 19% of the respondents admitted to current smoking. Although methodologic differences made comparison of knowledge of diet and cancer with the work of others difficult, knowledge of the risks of smoking was comparable to levels found in other studies.

Phase II trial of echinomycin in patients with advanced or recurrent colorectal cancer.

Echinomycin is a novel bifunctional intercalating agent derived from Streptomyces echinatus. A phase II clinical trial of echinomycin in patients with advanced, measurable colorectal cancer was initiated to determine the efficacy and toxicities of this agent. Echinomycin, 1.5 mg/m2, was given initially as a 30- to 60-min infusion every 4 weeks. After 4 episodes of anaphylaxis had occurred among the first 14 patients, the schedule was changed to a 24-h infusion, and an additional 16 patients were treated on this schedule. Treatment was given every 3 weeks. A total of 30 patients were eligible and evaluable; there were 3 (10%; 90% confidence interval, 3%-23%) clinical responses lasting 3, 3+, and 12 months, respectively. The most serious toxicity encountered was anaphylaxis, which occurred in 5 patients, although with no serious sequelae. A premedication regimen with dexamethasone, diphenhydramine, and cimetidine and a change of the duration of the infusion to 24 h reduced the incidence of this complication. Grade 2-3 vomiting occurred among earlier patients treated; however, with the 24-h schedule this toxicity was substantially reduced. The sole important case of hematologic toxicity was a single patient with grade 3 thrombocytopenia. Echinomycin employed in this dose and schedule had modest activity against colorectal cancer, comparable with that observed with 5-fluorouracil. Further studies in patients with gastrointestinal malignancies using a 24-h infusion with a dexamethasone premedication regimen similar to that employed prior to administration of taxol may be warranted.

Adjuvant radiotherapy for breast cancer as a risk factor for the development of lung cancer.

Women diagnosed with primary breast or lung cancer and recorded between 1972 and 1989 in our tumor registry were identified. Of 4,123 lung cancer patients and 3,537 breast cancer patients, 42 patients with both diagnoses were identified. The two malignancies were diagnosed simultaneously in five patients, lung cancer was diagnosed first in six patients and breast cancer was diagnosed first in 31 (p < 0.001). Nineteen of those 31 patients received adjuvant radiotherapy for breast cancer and developed lung cancer a median of 17 years later. Of the 19 irradiated patients who subsequently developed lung cancer, 15 did so in the ipsilateral lung and only four had lung cancer contralateral to the previously irradiated site (p < 0.001). Adjuvant radiotherapy for breast cancer as delivered decades ago may be an etiologic factor for lung cancer.

Weekly 5-fluorouracil combined with PALA: toxic and therapeutic effects in colorectal cancer.

A total of 51 patients (eight previously treated) received PALA added to 5-fluorouracil (5FU) given weekly. After 32 patients, the PALA schedule was changed from every other week to weekly, 24 hours preceding 5FU in accordance with preclinical leads (see text). Both schedules were associated with moderately severe toxic effects related primarily to PALA (skin rash) or to the combined effects of both drugs (diarrhea, vomiting, conjunctivitis, and neurotoxicity). Overall nine partial responses were observed, including three in patients previously treated with 5FU. However, future studies with this combination utilizing the current or other previously published schedules are not warranted in colorectal cancer. Since toxicity is a prominent impediment, the possibility of therapeutic synergy may perhaps be explored at drastically reduced doses of PALA, combined with other modulating measures.

BCNU (1,3-bis-(2-chloroethyl)-1-nitrosurea) lung. Drug-induced pulmonary changes.

The occurrence of pulmonary disease associated with long-term BCNU therapy is reported in two patients treated for astrocytoma grade II whose clinical presentations of pulmonary complications and corresponding tissue alterations showed striking differences. One patient presented with a dramatic, fulminating, and rapidly fatal pulmonary disease. His lungs revealed atypical proliferation of pneumocytes, moderate interstitial inflammation, fibrosis and intra-alveolar hyalin membranes. The second patient presented with slowly progressive dyspnea, ultimately leading to death secondary to severe diffuse alveolar septal fibrosis. Individual differences in response to toxicity are suggested and discussed.

Hypercalcemia in prostatic carcinoma. Report of eight cases.

Hypercalcemia is a rare complication of disseminated carcinoma of the prostate. To our knowledge, only three such patients have had their cases previously reported in the English language literature. Eight patients with prostatic cancer and hypercalcemia were seen at Montefiore Hospital and Medical Center, Bronx, NY, within the last six years. In six of the patients, the prostatic carcinoma exhibited unusual histologic patterns.

Effect of tamoxifen treatment on estrogen metabolism in postmenopausal women with advanced breast cancer.

The effect of tamoxifen therapy on plasma estrone and estradiol concentration, urinary excretion of estrone, estradiol, and estriol glucuronides, and metabolism of a tracer of 3H-estradiol was studied in 12 postmenopausal women with metastatic breast cancer. The most striking change observed was consistent increase in the 72-hour urinary recovery of total radioactivity after the tracer, from a mean of 47% to a mean of 61% of the dose. This increase was accounted for by a corresponding increase in the recovery of total glucuronide radioactivity, from a mean of 32% to a mean of 44% of the dose; there was no change in the proportions of estrone, estradiol, estriol, or 2-hydroxyestrone in the glucuronide fraction. The most likely explanation for this finding is that the estrogen-receptor-blocking effect of tamoxifen decreases estrogen uptake by various tissues and permits the estrogen to be excreted in the urine instead. There was also a small but consistent and significant decrease in plasma estrone (from 47 to 36 pg/ml) and estradiol (from 15 to 13 pg/ml), with no change in urinary excretion of estrogen glucuronides. The drop in plasma estrogen levels without a decrease in estrogen production suggests that tamoxifen may increase the metabolic and/or renal clearance of estrogen metabolites. There was no correlation between the observed effects of tamoxifen and the pretreatment estrogen-receptor status of the patient or her response to tamoxifen therapy.

Effect of tamoxifen treatment on cortisol metabolism and the course of the disease in advanced breast cancer.

Twenty-nine postmenopausal women with advanced breast cancer were treated with Tamoxifen, a nonsteroidal antiestrogen. The effect of the drug on the plasma concentration, production rate, and metabolism of cortisol was measured, and the relationship of the changes in these parameters to the course of the disease was investigated. After six weeks of Tamoxifen treatment the plasma cortisol concentration and the cortisol-binding globulin concentration increased by 26 and 64%, respectively, but the production rate of cortisol and the urinary excretion of its tetrahydro metabolites THF, ATHF, and THE decreased by 35 and 13%, respectively; all of these changes were statistically significant. When the group consisting of complete or partial responders was compared with one consisting of patients whose disease remained stable or worsened, no significant difference was detected between these two groups in the change in any of the above parameters. It was concluded that any improvement due to Tamoxifen was not related to changes in cortisol metabolism.

Long-term complete remissions of Kaposi's sarcoma with vinblastine therapy.

Four patients with advanced Kaposi's sarcoma who were treated with weekly vinblastine therapy achieved long-term remissions. Three patients are still in complete remission at two years, four years, and four years respectively, while the fourth achieved excellent partial remission lasting seven-and-one-half years. The regimen produced no toxicity. We suggest the use of vinblastine as a useful chemotherapeutic agent for Kaposi's sarcoma.

Adult Wilms tumor treated with radiotherapy and chemotherapy: a case report.

A 24-year-old man underwent a left radical nephrectomy for a mass that was found to be a Wilms tumor. The postoperative course, consisting of combined radiotherapy and chemotherapy, is discussed and the recent literature is reviewed.

Myelofibrosis associated with multiple myeloma.

Two patients had both multiple myeloma and myelofibrosis. One, who had both conditions, had autopsy confirmation of diagnosis three months later. The typical picture of agnogenic myeloid metasplasia with myelofibrosis developed in the second patient almost four years after the onset of k light chain myeloma. At this time all evidence of multiple myeloma had disappeared perhaps related to cyclophosphamide therapy. We were able to find two similar cases described in the English language literature. The two conditions may be related.