estramustine and Hypocalcemia

Treatment options for patients with hormone refractory prostate cancer (HRPC) showed unsatisfactory outcomes. Docetaxel-based combinations could offer more promising and tolerated results. A phase II trial was conducted with the combination of zoledronic acid, docetaxel and estramustine. Eligibility consisted of metastatic prostate adenocarcinoma with objective progression or rising prostate specific antigen levels (PSA) despite androgen deprivation therapy. Zoledronic acid was given at a dose of 4 mg on day 1, docetaxel (25 mg/m2) on days 1, 8 and 15, and estramustine orally at 140 mg two times daily on days 1 to 21 of a 28-day cycle. Twenty-seven patients were enrolled between October 2002 and November 2004. Median age was 68 years (53-83 years). A total of 124 cycles were administered with a median of 4.6 cycles per patient (1-8 cycles). The major toxicities were grades 1 to 3 anemia (55%), fatigue (15%), alopecia (11%) and hypocalcemia (11%). Two patients presented with deep venous thrombosis and died from pulmonary embolism. Another third patient died from Stevens-Johnson syndrome and grade 4 hepatic toxicity. Out of the 25 patients assessed for efficacy, 13 (52%) had a biologic response (>50% PSA decline). Three (21%) patients among the 14 with measurable disease had objective response: 1 complete response (CR) and 2 partial responses (PR). Response duration was 2 months for PR and 4 months for CR. A total of 12 patients (48%) experienced clinical benefit with pain reduction. This combination seemed effective; however toxic deaths especially from venous thrombosis counterbalanced the advantage of this regimen.

Topics: Administration, Oral; Aged; Aged, 80 and over; Alopecia; Anemia; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Diphosphonates; Docetaxel; Drug Administration Schedule; Drug Resistance, Neoplasm; Estramustine; Fatigue; Humans; Hypocalcemia; Imidazoles; Infusions, Intravenous; Injections, Intravenous; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Taxoids; Thrombocytopenia; Time Factors; Treatment Outcome; Zoledronic Acid

Topics: Aged; Aged, 80 and over; Estramustine; Humans; Hypocalcemia; Male; Parathyroid Hormone; Prostatic Neoplasms; Vitamin D; Vitamin D Deficiency

We describe a patient with androgen-independent prostate cancer in whom hypocalcemia developed during treatment with estramustine. The patient's total serum calcium level before and after the initiation of estramustine was 8.3 and 4.3 mg/dL, respectively (normal range 8.4 to 10.2). This finding prompted us to review the calcium levels in 135 consecutive patients who were also undergoing treatment with a similar estramustine-containing regimen. We found that hypocalcemia had developed in 20% of these patients during treatment. We speculate that estramustine may cause hypocalcemia by inhibiting the mobilization of calcium and the action of the parathyroid hormone in the skeleton.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Bone Neoplasms; Estramustine; Humans; Hypocalcemia; Incidence; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies

Topics: Aged; Aged, 80 and over; Estramustine; Humans; Hypocalcemia; Male; Myocardial Ischemia; Oxygen Inhalation Therapy; Pulmonary Edema