estramustine and taxane

The clinical significance of chemotherapy for patients with hormone refractory prostate cancer(HRPC) is still controversial. Some randomized-controlled trials represented that mitoxantrone combined with prednisone (or hydrocortisone) provided palliative benefit to patients with HRPC. These treatments are well tolerated by elderly patients. On the other hand, the high PSA response rates have been observed in trials with both estramustine and taxane, however, higher toxicity was also recognized. The most relevant endpoint is not only palliative efficacy but also survival in these trials. Recently, the improvement of survival with docetaxel-based chemotherapy was reported. Further studies with chemotherapeutic agents will be needed to provide patients of HRPC good quality of life and longer survival.

Topics: Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Bridged-Ring Compounds; Docetaxel; Drug Resistance; Drug Therapy, Combination; Estramustine; Humans; Male; Mitoxantrone; Neoplasms, Hormone-Dependent; Palliative Care; Prednisone; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Taxoids

The role of chemotherapy in prostate cancer continues to evolve. In men with symptomatic androgen-independent prostate cancer, significant reduction in pain and analgesic requirements are achievable with mitoxantrone and glucocorticoid combinations compared with glucocorticoids alone. However, survival rates are not improved. Taxane-based combinations with estramustine phosphate or other new agents show promise. Prostate-specific antigen response rates with these combinations appear to be 1.5 to 2 times more frequent than with mitoxantrone-based combinations. Randomized trials of taxane versus mitoxantrone-based therapies are underway. New agents and applications of current agents in adjuvant settings should be explored if survival in men with prostate cancer is to be improved.

Topics: Antineoplastic Agents; Antineoplastic Agents, Hormonal; Bridged-Ring Compounds; Calcitriol; Calcium Channel Agonists; Drug Therapy; Estramustine; Humans; Male; Mitoxantrone; Prostatic Neoplasms; Survival Rate; Taxoids

Androgen deprivation therapy remains the mainstay of therapy for patients with advanced prostate cancer and for selected patients with localized prostate cancer. Androgen deprivation therapy is the model of target-based therapies in this disease. Although it is clear that other target-based therapies need to be developed, cytotoxic chemotherapy is emerging as an effective form of treatment for men with prostate cancer. The early studies combining mitoxantrone plus a corticosteroid demonstrated that chemotherapy could be given to men with symptomatic hormone-refractory prostate cancer with minimal toxicity, and significant palliation could be provided. Since then, it has been recognized that estramustine, when combined with a variety of microtubular inhibitors, is very active in hormone-refractory prostate cancer. Doublets combining estramustine plus a taxane seem to be the most active. Although it appears that estramustine may add some activity to taxanes, the mechanism of its activity is uncertain, and its overall value is similarly questioned, particularly in light of its significant toxicity. Regimens that omit estramustine are being explored (ie, either taxane alone or taxane plus biologic agents). In addition, triplet therapy (combining estramustine plus a taxane plus a third drug, such as carboplatin or etoposide) is being explored. Finally, the utility of chemotherapy is beginning to be explored in the context of earlier disease in the neoadjuvant, adjuvant, or serologically relapsing group of patients. Data from these studies are just beginning to be gathered.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Chemotherapy, Adjuvant; Clinical Trials as Topic; Drug Administration Schedule; Drug Resistance, Neoplasm; Estramustine; Hormones; Humans; Male; Mitoxantrone; Neoplasm Metastasis; Prostatic Neoplasms; Taxoids

Estramustine is nornitrogen mustard linked to estradiol. It binds to tubulin and to microtubule-associated proteins, depolymerizes cytoplasmic microtubules, and disrupts the nuclear matrix. It has limited clinical activity as a single agent, but preclinical studies suggest that it is an effective modulator of antitubulins. This paper reviews the rationale for the combination of estramustine with antitubulins and the clinical toxicity profile of estramustine. Also discussed are data from phase II studies in hormone-resistant prostate cancer and in taxane-resistant breast cancer that suggest that the modulation of antitubulins by estramustine that has been demonstrated in vitro is indeed clinically relevant. Finally, current approaches to improving the tolerability of estramustine are described.

Topics: Breast Neoplasms; Bridged-Ring Compounds; Drug Therapy, Combination; Estramustine; Female; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms; Taxoids

This is a phase I/II trial of thalidomide with estramustine and paclitaxel in men with androgen-independent prostate cancer (AIPC) who underwent previous chemotherapy.. Men with progressive AIPC were treated with oral thalidomide (200 mg, 400 mg, or 600 mg daily), intravenous paclitaxel (100 mg/m2 over 3 hours on days 3 and 10), and oral estramustine (140 mg 3 times daily on days 1-5 and days 8-12) every 21 days.. Phase I: first cycle dose-limiting toxicity occurred in 0 of 3 patients at 200 mg thalidomide daily, 0 of 3 at 400 mg daily, and 1 of 3 at 600 mg daily (the designated maximum tolerated dose). Phase II: twenty-nine of 38 evaluable patients (76%; 95% confidence interval, 67%-87%) experienced a 50% decrease in prostate-specific antigen level. Five of 18 patients (28%) with measurable disease exhibited an objective response. Nine of 14 patients (64%) with disease refractory to previous taxane therapy had 50% decreases in prostate-specific antigen level. Grade 3/4 adverse events included neutropenia (9 of 39 [23%]), fatigue (9 of 39 [23%]), dyspnea (8 of 39 [21%]), and thromboembolic events (7 of 39 [18%]). Cumulative dose-limiting toxicity rates were minimal (13%) with thalidomide at 200 mg daily.. The profile of activity of thalidomide/paclitaxel/estramustine in taxane-refractory AIPC warrants further investigation.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Disease Progression; Estramustine; Humans; Male; Middle Aged; Neoplasms, Hormone-Dependent; Paclitaxel; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Rate; Taxoids; Thalidomide; Time Factors; Treatment Outcome

Estramustine phosphate (EMP) is an oral cytotoxic agent that depolymerizes tubuline, a mechanism of action that has been revisited during the last decade. Because of its lack of haematological toxicity and favourable tolerance profile, EMP is a good candidate for palliative chemotherapy. The aim of the study was to assess its tolerance and efficacy in advanced breast cancer after failure with usual regimens.. Patients with a life expectancy of at least 12 weeks and bi-dimensionally measurable disease having received at least 1 line of chemotherapy (including taxanes and/or anthracyclines) for advanced breast cancer (ABC) were eligible. EMP was given daily at a dose of 10 mg/kg until disease progression, unacceptable toxicity or patient refusal to continue chemotherapy.. Forty patients were included between June 1998 and December 1999. Patients had previously received one to eight chemotherapy regimens (median is two) for ABC. Twenty-two patients (55%) had visceral involvement and eighteen patients (45%) had osseous, chest wall or soft tissue metastases. Adverse events leading to early interruption of EMP were grade 2 allergy (n = 1), grade 2-3 nausea (n = 6), deep-vein thrombosis (n = 1), grade 3 sepsis (n = 1). One patient died at twenty-four weeks from pulmonary embolism, and another at fourteen weeks from unknown cause. Seven objective responses were observed (17.5%; 95% confidence interval (CI): 6%-30%). Median time to failure was 24 weeks (14-52+) in responding patients. All objective responses but one were observed in patients with visceral metastases. In 10 other patients (25%), disease remained stable with a median time to failure of 27 weeks (16-50); 6 of these experienced a decrease of consumption of analgesics or an improvement of performance status.. EMP is an active drug in ABC after failure with taxanes and anthracyclines, whose tolerance profile appears favourable.

Topics: Administration, Oral; Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Agents, Hormonal; Breast Neoplasms; Bridged-Ring Compounds; Disease Progression; Drug Resistance, Neoplasm; Estramustine; Female; Humans; Middle Aged; Salvage Therapy; Taxoids; Treatment Outcome

This case report demonstrates the effect of zoledronic acid (ZA) on a patient with bone metastatic hormone-refractory prostate cancer (HRPC) resistant to taxane, estramustine phosphate, carboplatin, and dexamethasone. The pathogenesis, diagnosis, and management of bone metastasis on HRPC are also reviewed.

Topics: Aged; Antineoplastic Agents, Hormonal; Bone Density Conservation Agents; Bone Neoplasms; Bridged-Ring Compounds; Carboplatin; Dexamethasone; Diphosphonates; Drug Resistance, Neoplasm; Estramustine; Humans; Imidazoles; Male; Prostatic Neoplasms; Taxoids; Zoledronic Acid

Epothilones and taxanes interfere with microtubule function. Ixabepilone, which is an epothilone-B analog, has activity against taxane-resistant cell lines and as first-line therapy for men with hormone-refractory prostate carcinoma (HRPC). Clinical cross-resistance of ixabepilone and taxanes in HRPC is unknown.. Records were evaluated retrospectively from patients with HRPC who were treated on a randomized Phase II trial of ixabepilone with or without estramustine and who subsequently received taxane chemotherapy. Posttherapy declines in prostate-specific antigen (PSA) levels and time to PSA progression were defined by consensus criteria. The median survival was evaluated by using the Kaplan-Meier method.. Forty-nine patients who received ixabepilone with estramustine (28 patients) or without estramustine (21 patients) subsequently received second-line taxane therapy. Second-line PSA declines > or = 50% were achieved by 51% of patients (95% confidence interval [95% CI], 33-66%). Second-line PSA declines > or = 50% were achieved by 61% of patients (95% CI, 42-78%) who achieved a first-line PSA decline > or = 50% with ixabepilone, compared with 33% of patients (95% CI, 13-59%) who did not (P = 0.08). Patients who discontinued first-line ixabepilone treatment for disease progression were less likely to achieve a PSA decline > or = 50% in response to second-line, taxane-based therapy compared with patients who discontinued for toxicity or patient preference (36% vs. 71%; P = 0.01).. Second-line taxane chemotherapy after ixabepilone resulted in a substantial frequency of PSA declines. Although patients with ixabepilone-refractory disease were less likely to respond to second-line taxane chemotherapy, 36% did achieve a PSA response. These findings were consistent with incomplete clinical cross-resistance between the taxanes and the epothilones.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Drug Resistance, Neoplasm; Epothilones; Estramustine; Humans; Male; Middle Aged; Neoplasms, Hormone-Dependent; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Taxoids; Treatment Outcome

Topics: Administration, Oral; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Drug Administration Schedule; Drug Resistance, Neoplasm; Drug Therapy, Combination; Estramustine; Humans; Male; Prostatic Neoplasms; Taxoids