Adriamycin and cyclophosphamide versus hydroxyurea in advanced prostatic cancer. A randomized Southwest Oncology Group study

Abstract

Over a 24‐month period, the Southwest Oncology Group (SWOG) conducted a randomized prospective chemotherapeutic trial in 158 patients with advanced prostatic cancer. Patients were initially randomized to receive either a combination of Adriamycin and cyclophosphamide (AC) or a single agent, hydroxyurea (H), and then crossed over to the other treatment on failure. Of the 137 evaluable patients, 43 (31%) had classically measurable metastatic disease in the lymph nodes, skin, chest, or liver. Focusing their efforts on this subset of patients with measurable disease, the authors of this report found the combination AC to have a superior response rate to the single agent, hydroxyurea. Objective response to AC was seen in 6 of 19 (32%) and in only one of 24 (4%) patients randomized to hydroxyurea (P = 0.06, Fisher's exact test). However, in the larger group of 137 evaluable patients, a survival advantage was not seen for those individuals treated with AC. Failure to demonstrate a survival advantage for an objectively superior drug combination would suggest the need for more active phase II agents in this disease.

HPMA Copolymer-Conjugated Pirarubicin in Multimodal Treatment of a Patient with Stage IV Prostate Cancer and Extensive Lung and Bone Metastases

“…Among them, anthracycline-based chemotherapy, including DOX and epirubicin, is frequently used, which suppresses anti-topoisomerase II activity [15], but systemic toxicities, especially cardiac toxicity, may occur. Although few data on anthracycline chemotherapy for prostate cancer are available, some reports state that survival or quality of life are improved during palliative care [16][17][18]. W h e n t h e c o m b i n a t i o n o f e p i r u b i c i n w i t h medroxyprogesterone (a luteinizing hormone) was compared with estramustine phosphate (a nitrogen mustard), the combination chemotherapy significantly increased the time to disease progression (median 7.6 vs. 4.3 months) [16].…”

Non-hormonal systemic therapy in men with hormone-refractory prostate cancer and metastases: a systematic review from the Cancer Care Ontario Program in Evidence-based Care's Genitourinary Cancer Disease Site Group

“…Anthracyclines are believed to exert their cytotoxic effects primarily through the inhibition of topoisomerase-II activity. Six RCTs examined anthracycline combinations [ 72 - 76 , 88 ] (Table 4 ). Four performed in the pre-PSA era compared doxorubicin-based cytotoxic chemotherapy regimens to non-doxorubicin-based regimens or single agents [ 74 - 76 ] or compared combined versus sequential 5-flourouracil-doxorubicin-mitomycin-C (FAM) [ 73 ].…”

“…Two trials compared anthracyclines to EMP [ 72 , 88 ]. The primary endpoints of those trials were tumor response and survival [ 73 - 76 ] and TTP [ 72 ].…”

“…Only one of five RCTs reporting overall survival data reported improved survival with chemotherapy [ 72 - 76 , 88 ] (Table 5 ). Laurie et al [ 73 ] randomized 142 patients to either combination chemotherapy with FAM or sequential chemotherapy with the same drugs (mitomycin C followed by doxorubicin followed by 5-fluorouracil).…”

Chemotherapy in Hormone Refractory Prostate Cancer

“…This is not surprising since no cytotoxic drug has shown remarkable single-agent activity and so a dramatic effect is unlikely to occur from combination of relatively inactive drugs, unless there is clinical synergy. In a Southwest Oncology Group study, patients were randomized to receive either doxorubicin plus cyclophosphamide in combination or hydroxyurea alone [11]. Twenty-six per cent of the patients on the combination arm and 13% on the single-agent arm had symptomatic improvements (P = 0.048).…”