Treatment of newly diagnosed metastatic prostate cancer patients with chemotherapy agents in combination with hormones versus hormones alone

Abstract

A prospective trial from July 1976 to September 1980 by the National Prostatic Cancer Project randomized newly diagnosed metastatic prostate cancer patients to DES 1 mg orally three times daily or orchiectomy; or DES, 1 mg, three times daily, plus cyclophosphamide at 1 mg/m2 iv every three weeks, or cyclophosphamide 1 g/m2 iv every three weeks plus estramustine phosphate (Estracyt) at 600 mg/m2 orally daily in three divided doses. There were 246 patients evaluated for response of 301 entered. These consisted of 83 on the DES/orchiectomy arm, 77 on DES plus cyclophosphamide, and 86 on Estracyt plus cyclophosphamide. Objective response rates, initially evaluated at 12 weeks, were similar among the treatments. However, chemotherapy as used in this study early in the diagnosis of metastatic disease appears to exhibit an improved effect on overall survival compared to hormone therapy alone. Analysis within groups having pain versus no pain at entry revealed a marked advantage after 80 weeks for chemotherapy when pain was initially present and a slight advantage during treatment (throughout follow‐up) when the pain was absent. Median survival times were 92, 91, and 94 weeks, respectively, for the three treatments. The progression‐free interval for responders showed no difference between initial treatments, although nearly one half of the patients are still in remission; hence, further follow‐up will be essential. Side effects were not excessive for the chemotherapy treatment arms and patient compliance was good. This national multicenter trial provides the basis for further testing of chemotherapy agents at an earlier phase for patients with newly diagnosed metastatic prostate cancer.

Combination of a long-acting delivery system for luteinizing hormone-releasing hormone agonist with Novantrone chemotherapy: increased efficacy in the rat prostate cancer model.

“…This approach, which makes the treatment more convenient and efficacious as compared with daily administration and ensures patient compliance, could become the method of choice for the endocrine treatment of advanced prostate carcinoma. Nevertheless, the duration of remissions may be limited, as hormonal manipulations do not prevent the ultimate growth of hormoneindependent cells (4)(5)(6)(7)(8)(9).…”

“…Chemotherapy inhibits the proliferation of androgen-independent cells. It is thus possible that the use of a combination of chemotherapeutic and hormonal approaches would prevent or delay a condition whereby hormone-insensitive cells present in the originally endocrine-dependent tumor become the predominant component (4)(5)(6)(7)(8)(9)(10)(11) (12).…”

“…It is well established for other hormonal methods of treatment that, in most patients with prostate cancer, the duration of remission may be limited and a relapse eventually occurs (5)(6)(7)(8)(9)(10)(11). Recently, one patient relapsed after 18 months of objective and subjective remission in response to [DTrp6]LH-RH treatment, in spite of continued blockade of pituitary-gonadal axis, and had to be treated by chemotherapy with cyclophosphamide (34).…”

Hormonal therapy and chemotherapy in patients with hormone-sensitive prostate cancer

“…Тот факт, что некоторые пациенты в тече-ние длительного времени отвечают на АДТ и им никогда не понадобится ХТ, стал основным аргумен-том против ранней ХТ. Для оценки эффективности ранней ХТ у больных гормоночувствительным РПЖ с начала 1980-х годов проведен ряд крупных исследо-ваний [30][31][32][33][34][35][36]. Ни одно из них не продемонстрирова-ло положительных результатов.…”

Disease-Specific Survival in Prostate Cancer Patients : Results from the Scandinavian Prostate Cancer Group (SPCG) Trial No. 5 and Regional Cancer Register Data

“…In their series of 21 consecutive patients "a noticeable improvement occurred in the clinical status of all but three patients". The response to ADT varies, with approximately 15% of men with metastatic disease primarily failing to respond to ADT [25,26,[28][29][30][31][32][33][34][35].…”