Is pretreatment hemoglobin level a predictor of complete response to salvage chemotherapy for recurrent platinum-pretreated ovarian carcinoma?

Purpose of investigation: The aim of this retrospective study was to correlate some patient characteristics at relapse, including also baseline hemoglobin levels, with complete response rate and survival following second-line chemotherapy for recurrent platinum-pretreated ovarian carcinoma.

Methods: The investigation was conducted on 63 patients who received salvage chemotherapy with different agents for clinically detectable recurrent ovarian carcinoma following initial surgery and first-line platinum-based chemotherapy. Some patient characteristics at relapse (patient age, serum CA 125 level, baseline hemoglobin level, number of recurrence sites, ascites, platinum-free interval, and treatment-free interval) were related to complete response rate to salvage chemotherapy and survival after recurrence. Median baseline hemoglobin level was 11.6 g/dl (range, 7.5-15.0 g/dl).

Results: Second-line chemotherapy obtained a complete response in 17 (27.0%) patients and a partial response in 11 (17.5%), whereas stable disease and progressive disease were detected in 19 (30.1%) and 16 (25.4%) patients, respectively. By univariate analysis, complete response rate was related to baseline hemoglobin level (p = 0.0019), platinum-free interval (p = 0.0012) and treatment-free interval (p = 0.0048). Multiple logistic regression showed that platinum-free interval (p = 0.0107) and baseline hemoglobin level (0.0312) were independent predictors of complete response. Patients with baseline hemoglobin levels >11.6 g/dl had a 5.338 higher chance of obtaining a complete response when compared to those with lower hemoglobin values. The platinum-free interval was the only independent prognostic variable for survival after recurrence (p = 0.0141), whereas baseline hemoglobin level was not related to survival at univariate nor at multivariate analysis.

Conclusions: Baseline hemoglobin level is an independent predictor of complete response to salvage chemotherapy in patients with recurrent platinum-pretreated ovarian carcinoma. Attention must be paid to anemia correction in these patients, with the aim of improving both the chance of response to salvage treatment and the quality of life.

Second-line chemotherapy; Recurrent ovarian carcinoma; Hemoglobin; Platinum

[1] McGuire W. P., Hoskins W. J., Brady M. F., Kucera P. R., Partridge E. E., Look K. Y. et al.: "Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer". N. Engl. J. Med., 1996, 334, 1.

[2] McGuire W. P., Ozols R. F.: "Chemotherapy of advanced ovarian cancer". Semin. Oneal., 1998, 25, 340.

[3] Conte P. F., Cianci C., Gadducci A.: "Up date in the management of advanced ovarian carcinoma". Crit. Rev. Oneal. Hematol., 1999, 32, 49.

[4] Garcia A. A.: "Salvage therapy for ovarian cancer". Curr. Oneal. Rep., 1999, 1, 64.

[5] Piccart M. J., Du Bois A., Gore M. E., Neijt J.P., Pecorelli S., Pujade-Lauraine E.: "A new standard of care for treatment of ovarian cancer". Eur. J. Cancer, 2000, 36, 10.

[6] Piccart M. J., Bertelsen K., James K., Cassidy J., Mangioni C., Simonsen E., Stuart G. et al.: "Randomized intergroup trial of scisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results". J. Natl. Cancer Inst., 2000, 92, 699.

[7] Neijt J. P., Engelholm S. A., Tuxen M. K., Sorensen P. G., Hansen M., Sessa C. et al.: "Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer". J. Clin. Oneal., 2000, 18, 3084.

[8] Ozols R. F.: "Paclitaxel (Taxol)/carboplatin combination chemotherapy in the treatment of advanced ovarian cancer". Semin. Oncol., 2000, 27 (suppl. 7), 3.

[9] Gadducci A., Conte P. F., Cianci C., Negri S., Genazzani A. R.: "Treatment options in patients with recurrent ovarian cancer" Anticancer Res., 2001, 21, 3557.

[10] Markman M., Rothman R., Hakes T., Reichman B., Hoskins W., Rubin S. et al.: "Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin". J. Clin. Oneal., 1991, 9, 389.

[11] Trimble E. L., Adams J. D., Vena D., Hawkins M. J., Friedman M. A., F isherman J. S. et al.: "Paclitaxel for platinum-refractory ovarian cancer: results from the first I 000 patients registered to National Cancer Institute Treatment Referral Center 9103". J. Clin. Oncol., 1993, 11, 2405.

[12] Eisenhauer E. A., ten Bokkel Huinink W.W., Swenerton K. D., Gianni L., Myles J., van der Burg M. E. et al.: "European-Canadian trial of paclitaxel in relapsed ovarian cancer: high versus low-dose and long versus short infusion". J. Clin. Oneal., 1994, 12, 2654.

[13] Gadducci A., Brunetti I., Muttini M. P., Fanucchi A., Dargenio F., Giannessi P. G., Conte P. F.: "Epidoxorubicin and lonidamine in refractory or recurrent epithelial ovarian cancer". Eur. J. Cancer, 1994, 30, 1432.

[14] Vermorken J .B., Kobierska A., van der Burg M. E., Chevallier B., Zanaboni F., ten Bokkel Huinink W.W. et al.: "High-dose epirubicin in platinum-pretreated patients with ovarian carcinoma: the EORTC-GCCG experience". Eur. J. Gynaecol. Oneal., 1995, 16, 433.

[15] Chollet P., Bensmaine M. A., Brienza S., Deloche C., Cure H., Caillet H., Cvitkovic E.: "Single agent activity of oxaliplatin in heavily pretreated advanced epithelial ovarian cancer". Ann. Oncol., 1996, 7, 1065.

[16] Lund B., Neijt J.P.: "Gemcitabine in cisplatin-resistant ovarian cancer". Semin. Oneal., 1996, 23 (suppl. 10), 72.

[17] ten Bokkel Huinink W., Gore M., Carmichael J.. Gordon A., Malfetano J., Hudson I. et al.: "Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer". J. Clin. Oneal., 1997, 15, 2183.

[18] Muggia F. M., Hainsworth J. D., Jeffers S., Miller P., Groshen S., Tan M. et al.: "Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation". J. Clin. Oneal., 1997, 15, 987.

[19] Trope C., Hogberg T., Kaern J., Bertelsen K., Bjorkholm E., Boman K. et al.: "Long-term results from a phase II study of single agent paclitaxel (Taxol) in previously platinum treated patients with advanced ovarian cancer: the Nordic experience". Ann. Oncol., 1998, 9, 1301.

[20] Bolis G., Parazzini F., Scarfone G., Villa A., Amoroso M., Polatti A. et al.: "Paclitaxel vs epidoxorubicin plus paclitaxel as secondline therapy for platinum-refractory and -resistant ovarian cancer. Gynecol. Oncol., 1999, 72, 60.

[21] Silver D. F., Piver M. S.: "Gemcitabine salvage chemotherapy for patients with gynecologic malignancies of the ovary, fallopian tube, and peritoneum". Am. J. Clin. Oncol., 1999, 22, 450.

[22] Colombo N., Parma G., Bocciolone L., Sideri M., Franchi D., Maggioni A.: "Role of chemotherapy in relapsed ovarian cancer". Crit. Rev. Oncol.. Hematol., 1999, 32, 221.

[23] Gordon A. N., Fleagle J. T., Guthrie D., Parkin D. E., Gore M., Lacave A. J., Mutch D.: "Interim analysis of a pha、e III randomized trial of Doxil/Caelyx (D) versus topotecan (T) in the treatment of patients with relapsed ovarian cancer". Proc. Am. Soc. Clin. Oneal., 2000, 19, 380, (abstract 1504)

[24] McGuire W. P., Blessing J. A., Bookman M.A., Lentz S. S., Dunton C. J.: "Topotecan has substantial antitumor activity as first-line salvage therapy in platinum-sensitive epithelial ovarian carcinoma: a Gynecologic Oncology Group study". J. Clin Oneal., 2000, 18, 1062.

[25] Piccart M. J., Green J. A., Jimenez Lacave A., Reed N., Vergote I., Benedetti-Panici P. et al.: " Oxaliplatin or paclitaxel in patients with platinum-pretreated advanced ovarian cancer: a randomized phase II study of the European Organization for Research and Treatment of Cancer Gynecology Group". J. Clin. Oncol., 2000, 18, 1193.

[26] Verschraegen C. F., Sittisomwong T., Kudelka A. P., Guedes E., Stager M., Nelson-Taylor T. et al.: "Docetaxel for patients with paclitaxel-resistant Mullerian carcinoma". J. Clin. Oneal., 2000, 18, 2733.

[27] Katsumata N., Tsunematsu R., Tanaka K., Terashima Y., Ogita S., Hoshiai H. et al.: "A phase II trial of docetaxel in platinum pretreated patients with advanced epithelial ovarian cancer: a Japanese cooperative study". Ann. Oncol., 2000, 11, 1531.

[28] Gordon A. N., Granai C. O., Rose P. G., Hainsworth J., Lopez A., Weissman C. et al.: "Phase II study of liposomal doxorubicin in platinum- and paclitaxel-refractory epithelial ovarian cancer". J. Clin. Oneal., 2000, 18, 3093.

[29] Thigpen J.T ., Vance R. B., KhansurT .: "Second-line chemotherapy for recurrent carcinoma of the ovary". Cancer, 1993, 71, 1559.

[30] Markman M., Bookman M.A.: "Second-line treatment of ovanan cancer". The Oncologist, 2000, 5, 26.

[31] Shamsunder S., Kumar L., Gupta S., Kumar S., Bhatia N., Singh R., Kochupillai V.: "Chemotherapy in recurrent epithelial ovarian cancer (EOC): an analysis of prognostic factors". J. Obstet Gynaecol. Res., 2000, 26, 215.

[32] Eisenhauer E. A., Vermorken J.B., van Glabbeke M.: "Predictors of response to subsequent chemotherapy in platinum pretreated ovarian cancer: a multivariate analysis of 704 patients". Ann Oncol., 1997, 8, 963.

[33] SafraT ., GroshenS ., JeffersS .,T sao-WeiD .D ., Zhou L., Muderspach L. et al.: "Treatment of patients with ovarian carcinoma with pegylated liposomal doxorubicin: analysis of toxicities and predictors of outcome". Cancer, 2001, 91, 90.

[34] Vaupel P., Thews 0., Hoeckel M.:'Treatment resistance of solid tumors:role of hypoxia and anemia". Med. Oneal., 2001, 18, 243.

[35] Groopman J. E., Itri L. M.: "Chemotherapy-induced anemia in adults: incidence and treatment". J. Natl. Cancer Inst., 1999, 91, 1616.

[36] Hensley M. L., Lebeau D., Leon L. F., Venkatraman E., Waltzman R., Sabbatini P. et al.: " Identification of risk factors for requiring transfusion during front-line chemotherapy for ovarian cancer". Gynecol. Oncol., 2001, 81, 485.

[37] Obermair A., Handisurya A., Kaider A., Sevelda P., Kolbl H., Gitsch G.: "The relationship of pretreatment serum hemoglobin level to the survival of epithelial ovarian carcinoma patients: a prospective review". Cancer, 1998, 83, 726.

[38] Peethambaram P. P., Long H. J.: "Second-line and subsequent therapy for ovarian carcinoma". Curr. Oneal. Rep., 2002, 4, 159.