A retrospective evaluation of second-line chemotherapy response in hormone-refractory prostate carcinoma: Second-line taxane-based therapy after first-line epothilone-B analog ixahepilone (BMS-247550) therapy Journal Article
| Authors: | Rosenberg, J. E.; Galsky, M. D.; Rohs, N. C.; Weinberg, V. K.; Oh, W. K.; Kelly, W. K.; Small, E. J. |
| Article Title: | A retrospective evaluation of second-line chemotherapy response in hormone-refractory prostate carcinoma: Second-line taxane-based therapy after first-line epothilone-B analog ixahepilone (BMS-247550) therapy |
| Abstract: | BACKGROUND. 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. METHODS. 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. RESULTS. 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 ≥ 50% were achieved by 51% of patients (95% confidence interval [95% CI], 33-66%). Second-line PSA declines ≥ 50% were achieved by 61% of patients (95% CI, 42-78%) who achieved a first-line PSA decline ≥ 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 ≥ 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). CONCLUSIONS. 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. © 2005 American Cancer Society. |
| Keywords: | adult; cancer chemotherapy; clinical article; controlled study; treatment outcome; aged; aged, 80 and over; middle aged; survival rate; retrospective studies; clinical trial; disease course; side effect; paclitaxel; prostate specific antigen; carboplatin; controlled clinical trial; randomized controlled trial; antineoplastic combined chemotherapy protocols; cell line; calcitriol; drug resistance, neoplasm; retrospective study; docetaxel; prostate-specific antigen; prostatic neoplasms; taxoids; kaplan meier method; taxane derivative; microtubule; hormone resistance; ixabepilone; epothilones; taxanes; epothilone b; prostate carcinoma; neoplasms, hormone-dependent; cross resistance; bridged compounds; estramustine; multidrug resistance protein; hormone-refractory prostate carcinoma; multidrug-resistance protein |
| Journal Title: | Cancer |
| Volume: | 106 |
| Issue: | 1 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2006-01-01 |
| Start Page: | 58 |
| End Page: | 62 |
| Language: | English |
| DOI: | 10.1002/cncr.21559 |
| PUBMED: | 16329138 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 22" - "Export Date: 4 June 2012" - "CODEN: CANCA" - "Source: Scopus" |
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