Results of a phase II study with doxorubicin, etoposide, and cisplatin in patients with fully characterized small-cell carcinoma of the prostate.
OBJECTIVE
To determine the activity and toxicity of doxorubicin in combination with cisplatin and etoposide in patients with small-cell prostate carcinoma (SCPCa) and to characterize the clinicopathologic features of SCPCa.


METHODS
Patients with SCPCa (pure or mixed), measurable disease, good organ function, and no prior treatment with doxorubicin, etoposide, or cisplatin were treated every 4 weeks with doxorubicin 50 mg/m(2) as a 24-hour intravenous (IV) infusion followed by etoposide 120 mg/m(2)/d and cisplatin 25 mg/m(2)/d IV on days 2 to 4.


RESULTS
Thirty-eight patients (36 assessable for response) were treated for a median of four cycles. Twenty-nine (81%) of 36 patients had prior hormonal therapy. Study patients had visceral metastases, lytic bone disease, and relatively low serum prostate-specific antigen (PSA). We observed 22 partial responses (response rate, 61% in an intent-to-treat analysis); toxicity was severe (grade 3 or 4 neutropenia 100%, thrombocytopenia 66%, mucositis 21%, and infection 68%). Three patients died of toxicity. Median time to progression and overall survival time were 5.8 months and 10.5 months, respectively. Performance status, serum albumin, and number of organs involved (but not PSA, carcinoembryonic antigen, or neuroendocrine markers) were predictors of survival.


CONCLUSIONS
SCPCa presents unique clinicopathologic features. Addition of doxorubicin to the etoposide/cisplatin regimen caused higher toxicity in this patient population and failed to improve outcome. Given these results, we do not recommend further development of this regimen for patients with SCPCa. Improvement in therapy will come from understanding the biology of SCPCa progression and integrating new targeted therapies into the treatment of SCPCa.
Papandreou
Christos N
CN
Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. cpapandr@notes.mdacc.tmc.edu
Daliani
Danai D
DD
Thall
Peter F
PF
Tu
Shi-Ming
SM
Wang
Xuemei
X
Reyes
Adriana
A
Troncoso
Patricia
P
Logothetis
Christopher J
CJ
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D018288:Carcinoma, Small Cell / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D005047:Etoposide; D004317:Doxorubicin; D002945:Cisplatin