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Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

Sustained platelet-sparing effect of weekly low dose paclitaxel allows effective, tolerable delivery of extended dose dense weekly carboplatin in platinum resistant/refractory epithelial ovarian cancer

Authors: Rohini Sharma, Janet Graham, Sarah Blagden, Hani Gabra

Published in: BMC Cancer | Issue 1/2011

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Abstract

Background

Platinum agents have shown demonstrable activity in the treatment of patients with platinum resistant, recurrent ovarian cancer when delivered in a "dose-dense" fashion. However, the development of thrombocytopenia limits the weekly administration of carboplatin to no greater than AUC 2. Paclitaxel has a well-described platelet sparing effect however its use to explicitly provide thromboprotection in the context of dose dense carboplatin has not been explored.

Methods

We treated seven patients with platinum resistant ovarian cancer who had previously received paclitaxel or who had developed significant peripheral neuropathy precluding the use of further full dose weekly paclitaxel.

Results

We were able to deliver carboplatin AUC 3 and paclitaxel 20 mg/m2 with no thrombocytopenia or worsening of neuropathic side-effects, and with good activity.

Conclusions

We conclude that this regimen may be feasible and active, and could be formally developed as a "platinum-focussed dose-dense scaffold" into which targeted therapies that reverse platinum resistance can be incorporated, and merits further evaluation.
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Literature
1.
go back to reference Piver MS, Baker TR, Piedmonte M, Sandecki AM: Epidemiology and etiology of ovarian cancer. Semin Oncol. 1991, 18 (3): 177-185.PubMed Piver MS, Baker TR, Piedmonte M, Sandecki AM: Epidemiology and etiology of ovarian cancer. Semin Oncol. 1991, 18 (3): 177-185.PubMed
2.
go back to reference Neijt JP, ten Bokkel Huinink WW, van der Burg ME, van Oosterom AT, Willemse PH, Vermorken JB, van Lindert AC, Heintz AP, Aartsen E, van Lent M, et al: Long-term survival in ovarian cancer. Mature data from The Netherlands Joint Study Group for Ovarian Cancer. Eur J Cancer. 1991, 27 (11): 1367-1372. 10.1016/0277-5379(91)90011-2.CrossRefPubMed Neijt JP, ten Bokkel Huinink WW, van der Burg ME, van Oosterom AT, Willemse PH, Vermorken JB, van Lindert AC, Heintz AP, Aartsen E, van Lent M, et al: Long-term survival in ovarian cancer. Mature data from The Netherlands Joint Study Group for Ovarian Cancer. Eur J Cancer. 1991, 27 (11): 1367-1372. 10.1016/0277-5379(91)90011-2.CrossRefPubMed
3.
go back to reference Angioli R, Palaia I, Damiani P, Montera R, Benedetti Panici P: [Up-date on cytoreductive surgery in the management of advanced ovarian cancer]. Minerva Ginecol. 2006, 58 (6): 459-470.PubMed Angioli R, Palaia I, Damiani P, Montera R, Benedetti Panici P: [Up-date on cytoreductive surgery in the management of advanced ovarian cancer]. Minerva Ginecol. 2006, 58 (6): 459-470.PubMed
4.
go back to reference Markman M, Rothman R, Hakes T, Reichman B, Hoskins W, Rubin S, Jones W, Almadrones L, Lewis JL: Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin. J Clin Oncol. 1991, 9 (3): 389-393.PubMed Markman M, Rothman R, Hakes T, Reichman B, Hoskins W, Rubin S, Jones W, Almadrones L, Lewis JL: Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin. J Clin Oncol. 1991, 9 (3): 389-393.PubMed
5.
go back to reference van der Burg ME, Hoff AM, van Lent M, Rodenburg CJ, van Putten WL, Stoter G: Carboplatin and cyclophosphamide salvage therapy for ovarian cancer patients relapsing after cisplatin combination chemotherapy. Eur J Cancer. 1991, 27 (3): 248-250. 10.1016/0277-5379(91)90507-A.CrossRefPubMed van der Burg ME, Hoff AM, van Lent M, Rodenburg CJ, van Putten WL, Stoter G: Carboplatin and cyclophosphamide salvage therapy for ovarian cancer patients relapsing after cisplatin combination chemotherapy. Eur J Cancer. 1991, 27 (3): 248-250. 10.1016/0277-5379(91)90507-A.CrossRefPubMed
6.
go back to reference Eisenhauer EA, ten Bokkel Huinink WW, Swenerton KD, Gianni L, Myles J, van der Burg ME, Kerr I, Vermorken JB, Buser K, Colombo N, et al: European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high-dose versus low-dose and long versus short infusion. J Clin Oncol. 1994, 12 (12): 2654-2666.PubMed Eisenhauer EA, ten Bokkel Huinink WW, Swenerton KD, Gianni L, Myles J, van der Burg ME, Kerr I, Vermorken JB, Buser K, Colombo N, et al: European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high-dose versus low-dose and long versus short infusion. J Clin Oncol. 1994, 12 (12): 2654-2666.PubMed
7.
go back to reference van der Burg ME, van der Gaast A, Vergote I, Burger CW, van Doorn HC, de Wit R, Stoter G, Verweij J: What is the role of dose-dense therapy?. Int J Gynecol Cancer. 2005, 15 (Suppl 3): 233-240.CrossRefPubMed van der Burg ME, van der Gaast A, Vergote I, Burger CW, van Doorn HC, de Wit R, Stoter G, Verweij J: What is the role of dose-dense therapy?. Int J Gynecol Cancer. 2005, 15 (Suppl 3): 233-240.CrossRefPubMed
8.
go back to reference Vasey PA: "Dose dense" chemotherapy in ovarian cancer. Int J Gynecol Cancer. 2005, 15 (Suppl 3): 226-232.CrossRefPubMed Vasey PA: "Dose dense" chemotherapy in ovarian cancer. Int J Gynecol Cancer. 2005, 15 (Suppl 3): 226-232.CrossRefPubMed
9.
go back to reference Simon R, Norton L: The Norton-Simon hypothesis: designing more effective and less toxic chemotherapeutic regimens. Nat Clin Pract Oncol. 2006, 3 (8): 406-407.CrossRefPubMed Simon R, Norton L: The Norton-Simon hypothesis: designing more effective and less toxic chemotherapeutic regimens. Nat Clin Pract Oncol. 2006, 3 (8): 406-407.CrossRefPubMed
10.
go back to reference Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, Davidson NE, Martino S, Livingston R, Ingle JN, et al: Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003, 21 (8): 1431-1439. 10.1200/JCO.2003.09.081.CrossRefPubMed Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, Davidson NE, Martino S, Livingston R, Ingle JN, et al: Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003, 21 (8): 1431-1439. 10.1200/JCO.2003.09.081.CrossRefPubMed
11.
go back to reference Katsumata N, Yasuda M, Takahashi F, Isonishi S, Jobo T, Aoki D, Tsuda H, Sugiyama T, Kodama S, Kimura E, et al: Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009, 374 (9698): 1331-1338. 10.1016/S0140-6736(09)61157-0.CrossRefPubMed Katsumata N, Yasuda M, Takahashi F, Isonishi S, Jobo T, Aoki D, Tsuda H, Sugiyama T, Kodama S, Kimura E, et al: Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009, 374 (9698): 1331-1338. 10.1016/S0140-6736(09)61157-0.CrossRefPubMed
12.
go back to reference Fujiwara K, Aotani E, Hamano T, Nagao S, Yoshikawa H, Sugiyama T, Kigawa J, Aoki D, Katsumata N, Takeuchi M, et al: A randomized Phase II/III trial of 3 weekly intraperitoneal versus intravenous carboplatin in combination with intravenous weekly dose-dense paclitaxel for newly diagnosed ovarian, fallopian tube and primary peritoneal cancer. Jpn J Clin Oncol. 41 (2): 278-282. Fujiwara K, Aotani E, Hamano T, Nagao S, Yoshikawa H, Sugiyama T, Kigawa J, Aoki D, Katsumata N, Takeuchi M, et al: A randomized Phase II/III trial of 3 weekly intraperitoneal versus intravenous carboplatin in combination with intravenous weekly dose-dense paclitaxel for newly diagnosed ovarian, fallopian tube and primary peritoneal cancer. Jpn J Clin Oncol. 41 (2): 278-282.
13.
go back to reference Daga H, Isobe T, Miyazaki M, Fujitaka K, Kondo K, Kohno N: Investigating the relationship between serum thrombopoietin kinetics and the platelet-sparing effect: A clinical pharmacological evaluation of combined paclitaxel and carboplatin in patients with non-small cell lung cancer. Oncol Rep. 2004, 11 (6): 1225-1231.PubMed Daga H, Isobe T, Miyazaki M, Fujitaka K, Kondo K, Kohno N: Investigating the relationship between serum thrombopoietin kinetics and the platelet-sparing effect: A clinical pharmacological evaluation of combined paclitaxel and carboplatin in patients with non-small cell lung cancer. Oncol Rep. 2004, 11 (6): 1225-1231.PubMed
14.
go back to reference van Warmerdam LJ, Huizing MT, Giaccone G, Postmus PE, ten Bokkel Huinink WW, van Zandwijk N, Koolen MG, Helmerhorst TJ, van der Vijgh WJ, Veenhof CH, et al: Clinical pharmacology of carboplatin administered in combination with paclitaxel. Semin Oncol. 1997, 24 (1 Suppl 2): S2-97-S92-104 van Warmerdam LJ, Huizing MT, Giaccone G, Postmus PE, ten Bokkel Huinink WW, van Zandwijk N, Koolen MG, Helmerhorst TJ, van der Vijgh WJ, Veenhof CH, et al: Clinical pharmacology of carboplatin administered in combination with paclitaxel. Semin Oncol. 1997, 24 (1 Suppl 2): S2-97-S92-104
15.
go back to reference Ishikawa H, Fujiwara K, Suzuki S, Tanaka Y, Kohno I: Platelet-sparing effect of paclitaxel in heavily pretreated ovarian cancer patients. Int J Clin Oncol. 2002, 7 (5): 330-333.PubMed Ishikawa H, Fujiwara K, Suzuki S, Tanaka Y, Kohno I: Platelet-sparing effect of paclitaxel in heavily pretreated ovarian cancer patients. Int J Clin Oncol. 2002, 7 (5): 330-333.PubMed
16.
go back to reference Akerley W, Rathore R, Ready N, Leone L, Sikov W, Safran H, Kennedy T: A phase I study of a weekly schedule of paclitaxel and carboplatin in patients with advanced carcinoma. Cancer. 2002, 95 (9): 2000-2005. 10.1002/cncr.10902.CrossRefPubMed Akerley W, Rathore R, Ready N, Leone L, Sikov W, Safran H, Kennedy T: A phase I study of a weekly schedule of paclitaxel and carboplatin in patients with advanced carcinoma. Cancer. 2002, 95 (9): 2000-2005. 10.1002/cncr.10902.CrossRefPubMed
17.
go back to reference Sehouli J, Stengel D, Elling D, Ortmann O, Blohmer J, Riess H, Lichtenegger W: First-line chemotherapy with weekly paclitaxel and carboplatin for advanced ovarian cancer: a phase I study. Gynecol Oncol. 2002, 85 (2): 321-326. 10.1006/gyno.2002.6623.CrossRefPubMed Sehouli J, Stengel D, Elling D, Ortmann O, Blohmer J, Riess H, Lichtenegger W: First-line chemotherapy with weekly paclitaxel and carboplatin for advanced ovarian cancer: a phase I study. Gynecol Oncol. 2002, 85 (2): 321-326. 10.1006/gyno.2002.6623.CrossRefPubMed
18.
go back to reference Calvert AH, Newell DR, Gumbrell LA, O'Reilly S, Burnell M, Boxall FE, Siddik ZH, Judson IR, Gore ME, Wiltshaw E: Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol. 1989, 7 (11): 1748-1756.PubMed Calvert AH, Newell DR, Gumbrell LA, O'Reilly S, Burnell M, Boxall FE, Siddik ZH, Judson IR, Gore ME, Wiltshaw E: Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol. 1989, 7 (11): 1748-1756.PubMed
19.
go back to reference Swisher EM, Mutch DG, Rader JS, Elbendary A, Herzog TJ: Topotecan in platinum- and paclitaxel-resistant ovarian cancer. Gynecol Oncol. 1997, 66 (3): 480-486. 10.1006/gyno.1997.4787.CrossRefPubMed Swisher EM, Mutch DG, Rader JS, Elbendary A, Herzog TJ: Topotecan in platinum- and paclitaxel-resistant ovarian cancer. Gynecol Oncol. 1997, 66 (3): 480-486. 10.1006/gyno.1997.4787.CrossRefPubMed
20.
21.
go back to reference Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ: Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol. 2001, 19 (14): 3312-3322.PubMed Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ: Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol. 2001, 19 (14): 3312-3322.PubMed
22.
go back to reference de Jongh FE, de Wit R, Verweij J, Sparreboom A, van den Bent MJ, Stoter G, van der Burg ME: Dose-dense cisplatin/paclitaxel. a well-tolerated and highly effective chemotherapeutic regimen in patients with advanced ovarian cancer. Eur J Cancer. 2002, 38 (15): 2005-2013. 10.1016/S0959-8049(02)00242-3.CrossRefPubMed de Jongh FE, de Wit R, Verweij J, Sparreboom A, van den Bent MJ, Stoter G, van der Burg ME: Dose-dense cisplatin/paclitaxel. a well-tolerated and highly effective chemotherapeutic regimen in patients with advanced ovarian cancer. Eur J Cancer. 2002, 38 (15): 2005-2013. 10.1016/S0959-8049(02)00242-3.CrossRefPubMed
23.
go back to reference Van der Burg ME, et al: Phase II study of weekly paclitaxel carboplatin in the treatment of progressive ovarian cancer. Journal of Clinical Oncology. 2004, 22 (14S): 5058- Van der Burg ME, et al: Phase II study of weekly paclitaxel carboplatin in the treatment of progressive ovarian cancer. Journal of Clinical Oncology. 2004, 22 (14S): 5058-
24.
go back to reference Sharma R, Graham J, Mitchell H, Brooks A, Blagden S, Gabra H: Extended weekly dose-dense paclitaxel/carboplatin is feasible and active in heavily pre-treated platinum-resistant recurrent ovarian cancer. Br J Cancer. 2009, 100 (5): 707-712. 10.1038/sj.bjc.6604914.CrossRefPubMedPubMedCentral Sharma R, Graham J, Mitchell H, Brooks A, Blagden S, Gabra H: Extended weekly dose-dense paclitaxel/carboplatin is feasible and active in heavily pre-treated platinum-resistant recurrent ovarian cancer. Br J Cancer. 2009, 100 (5): 707-712. 10.1038/sj.bjc.6604914.CrossRefPubMedPubMedCentral
25.
go back to reference Pertusini E, Ratajczak J, Majka M, Vaughn D, Ratajczak MZ, Gewirtz AM: Investigating the platelet-sparing mechanism of paclitaxel/carboplatin combination chemotherapy. Blood. 2001, 97 (3): 638-644. 10.1182/blood.V97.3.638.CrossRefPubMed Pertusini E, Ratajczak J, Majka M, Vaughn D, Ratajczak MZ, Gewirtz AM: Investigating the platelet-sparing mechanism of paclitaxel/carboplatin combination chemotherapy. Blood. 2001, 97 (3): 638-644. 10.1182/blood.V97.3.638.CrossRefPubMed
26.
go back to reference Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, Wheeler S, Swart AM, Qian W, Torri V, et al: Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet. 2003, 361 (9375): 2099-2106.CrossRefPubMed Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, Wheeler S, Swart AM, Qian W, Torri V, et al: Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet. 2003, 361 (9375): 2099-2106.CrossRefPubMed
27.
go back to reference Stronach EA, Rama N, Gabra H: Identification of functional modulators of platinum resistance using isogenically matched ovarian cancer cell line models. 2008 AACR Annual Meeting: 2008; San Diego: Proc of the 99th Annual Meeting of the American Association for Cancer Research. 2008 Stronach EA, Rama N, Gabra H: Identification of functional modulators of platinum resistance using isogenically matched ovarian cancer cell line models. 2008 AACR Annual Meeting: 2008; San Diego: Proc of the 99th Annual Meeting of the American Association for Cancer Research. 2008
28.
go back to reference Linch M, Stavridi F, Hook J, Barbachano Y, Gore M, Kaye SB: Experience in a UK cancer centre of weekly paclitaxel in the treatment of relapsed ovarian and primary peritoneal cancer. Gynecol Oncol. 2008, 109 (1): 27-32. 10.1016/j.ygyno.2008.01.007.CrossRefPubMed Linch M, Stavridi F, Hook J, Barbachano Y, Gore M, Kaye SB: Experience in a UK cancer centre of weekly paclitaxel in the treatment of relapsed ovarian and primary peritoneal cancer. Gynecol Oncol. 2008, 109 (1): 27-32. 10.1016/j.ygyno.2008.01.007.CrossRefPubMed
Metadata
Title
Sustained platelet-sparing effect of weekly low dose paclitaxel allows effective, tolerable delivery of extended dose dense weekly carboplatin in platinum resistant/refractory epithelial ovarian cancer
Authors
Rohini Sharma
Janet Graham
Sarah Blagden
Hani Gabra
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-289

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