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Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Oxaliplatin plus leucovorin and 5-fluorouracil (FOLFOX-4) as a salvage chemotherapy in heavily-pretreated platinum-resistant ovarian cancer

Authors: Vincenza Conteduca, Giorgia Gurioli, Lorena Rossi, Emanuela Scarpi, Cristian Lolli, Giuseppe Schepisi, Alberto Farolfi, Delia De Lisi, Valentina Gallà, Salvatore Luca Burgio, Cecilia Menna, Andrea Amadori, Lorena Losi, Dino Amadori, Maria Paola Costi, Ugo De Giorgi

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

The purpose of this study was to evaluate the clinical impact of oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX-4) chemotherapy in terms of the response rate, progression-free/overall survival (PFS/OS) and safety profile in patients with heavily pretreated recurrent epithelial ovarian cancer.

Methods

Clinical data were reviewed in 29 patients who received FOLFOX-4 as more than third-line chemotherapy, consisting of 85 mg/m2 of oxaliplatin, 200 mg/m2 of leucovorin, and bolus 400 mg/m2 on day 1 of 5-fluorouracil, followed by a 22-h infusion of 600 mg/m2 of 5-fluorouracil for 2 consecutive days every 3 weeks. We also compared the efficacy and toxicity of FOLFOX-4 with that of topotecan, a standard treatment, given at a dosage of 1.5 mg/m2 every three weeks in 26 patients.

Results

The median age of enrolled patients was 60 years (range 33 to 85). A median of 4 cycles (range 1–17) of FOLFOX-4 were administered. Complete response and partial response were observed in one (3.5%) and 5 (17.2.2%) patients, respectively, while stable disease was reported in 8 (27.6%) patients. Among all patients, grade 3–4 anemia, neutropenia, and thrombocytopenia were observed in 0 (0%), 5 (17.2%), and 3 (10.3%) cases, respectively. Grade 3–4 fatigue was recorded in one (3.4%) patient and diarrhea in 2 (6.9%). Median PFS and OS were 2.8 months [95% confidence interval (CI) 1.7–4.9] and 6.2 months (95% CI 2.4–14.6), respectively. No significant differences in terms of efficacy and toxicity were observed between patients receiving FOLFOX-4 and those treated with topotecan.

Conclusions

The FOLFOX-4 regimen would seem to obtain similar survival rates to those of standard therapy with topotecan in platinum-resistant ovarian cancer. Further randomized trials are warranted to confirm our findings.
Literature
1.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Cancer statistics, 2011. CA Cancer J Clin. 2011;61:69–90.CrossRef Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Cancer statistics, 2011. CA Cancer J Clin. 2011;61:69–90.CrossRef
2.
go back to reference Hennessy BT, Coleman RL, Markman M. Ovarian cancer. Lancet 2009;17;374(9698):1371–1382. Hennessy BT, Coleman RL, Markman M. Ovarian cancer. Lancet 2009;17;374(9698):1371–1382.
3.
go back to reference Pignata S, Cecere S, Du Bois A, Harter P, Heitz F. Treatment of recurrent ovarian cancer. Ann Oncol. 2017;8(Suppl 8):viii51–6.CrossRef Pignata S, Cecere S, Du Bois A, Harter P, Heitz F. Treatment of recurrent ovarian cancer. Ann Oncol. 2017;8(Suppl 8):viii51–6.CrossRef
4.
go back to reference Raymond E, Chaney SG, Taamma A, Cvitkovic E. Oxaliplatin: a review of preclinical and clinical studies. Ann Oncol. 1998;9:1053–71.CrossRef Raymond E, Chaney SG, Taamma A, Cvitkovic E. Oxaliplatin: a review of preclinical and clinical studies. Ann Oncol. 1998;9:1053–71.CrossRef
5.
go back to reference Rixe O, Ortuzar W, Alvarez M, Parker R, Reed E, Paull K, et al. Oxaliplatin, tetraplatin, cisplatin, and carboplatin: spectrum of activity in drug-resistant cell lines and in the cell lines of the National Cancer Institute's anticancer drug screen panel. Biochem Pharmacol. 1996;52:1855–65.CrossRef Rixe O, Ortuzar W, Alvarez M, Parker R, Reed E, Paull K, et al. Oxaliplatin, tetraplatin, cisplatin, and carboplatin: spectrum of activity in drug-resistant cell lines and in the cell lines of the National Cancer Institute's anticancer drug screen panel. Biochem Pharmacol. 1996;52:1855–65.CrossRef
6.
go back to reference Chollet P, Bensmaine MA, Brienza S, Deloche C, Curé H, Caillet H, et al. Single agent activity of oxaliplatin in heavily pretreated advanced epithelial ovarian cancer. Ann Oncol. 1996;7:1065–70.CrossRef Chollet P, Bensmaine MA, Brienza S, Deloche C, Curé H, Caillet H, et al. Single agent activity of oxaliplatin in heavily pretreated advanced epithelial ovarian cancer. Ann Oncol. 1996;7:1065–70.CrossRef
7.
go back to reference Soulie P, Bensmaine A, Garrino C, Chollet P, Brain E, Fereres M, et al. Oxaliplatin/cisplatin (l-OHP/CDDP) combination in heavily pretreated ovarian cancer. Eur J Cancer. 1997;33:1400–6.CrossRef Soulie P, Bensmaine A, Garrino C, Chollet P, Brain E, Fereres M, et al. Oxaliplatin/cisplatin (l-OHP/CDDP) combination in heavily pretreated ovarian cancer. Eur J Cancer. 1997;33:1400–6.CrossRef
8.
go back to reference Piccart MJ, Green JA, Lacave AJ, 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;18:1193–202.CrossRef Piccart MJ, Green JA, Lacave AJ, 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;18:1193–202.CrossRef
9.
go back to reference Fracasso PM, Blessing JA, Morgan MA, Sood AK, Hoffman JS. Phase II study of oxaliplatin in platinum-resistant and refractory ovarian cancer: a gynecologic group study. J Clin Oncol. 2003;21:2856–9.CrossRef Fracasso PM, Blessing JA, Morgan MA, Sood AK, Hoffman JS. Phase II study of oxaliplatin in platinum-resistant and refractory ovarian cancer: a gynecologic group study. J Clin Oncol. 2003;21:2856–9.CrossRef
10.
go back to reference Prefontaine M, Donovan JT, Powell JL, Buley L. Treatment of refractory ovarian cancer with 5-fluorouracil and leucovorin. Gynecol Oncol. 1996;61:249–52.CrossRef Prefontaine M, Donovan JT, Powell JL, Buley L. Treatment of refractory ovarian cancer with 5-fluorouracil and leucovorin. Gynecol Oncol. 1996;61:249–52.CrossRef
11.
go back to reference Morgan RJ Jr, Speyer J, Doroshow JH, Margolin K, Raschko J, Sorich J, et al. Modulation of 5-fluorouracil with high-dose leucovorin calcium: activity in ovarian cancer and correlation with CA-125 levels. Gynecol Oncol. 1995;58:79–85.CrossRef Morgan RJ Jr, Speyer J, Doroshow JH, Margolin K, Raschko J, Sorich J, et al. Modulation of 5-fluorouracil with high-dose leucovorin calcium: activity in ovarian cancer and correlation with CA-125 levels. Gynecol Oncol. 1995;58:79–85.CrossRef
12.
go back to reference Look KY, Muss HB, Blessing JA, Morris M. A phase II trial of 5-fluorouracil and high-dose leucovorin in recurrent epithelial ovarian carcinoma. A Gynecologic Oncology Group Study Am J Clin Oncol. 1995;18:9–22. Look KY, Muss HB, Blessing JA, Morris M. A phase II trial of 5-fluorouracil and high-dose leucovorin in recurrent epithelial ovarian carcinoma. A Gynecologic Oncology Group Study Am J Clin Oncol. 1995;18:9–22.
13.
go back to reference Kamphuis JT, Huider MC, Ras GJ, Verhagen CA, Kateman I, Vreeswijk JH, et al. High-dose 5-fluorouracil and leucovorin as second-line chemotherapy in patients with platinum resistant epithelial ovarian cancer. Cancer Chemother Pharmacol. 1995;37:190–2.CrossRef Kamphuis JT, Huider MC, Ras GJ, Verhagen CA, Kateman I, Vreeswijk JH, et al. High-dose 5-fluorouracil and leucovorin as second-line chemotherapy in patients with platinum resistant epithelial ovarian cancer. Cancer Chemother Pharmacol. 1995;37:190–2.CrossRef
14.
go back to reference Long HJ 3rd, Nelimark RA, Su JQ, Garneau SC, Levitt R, Goldberg RM, et al. Phase II evaluation of 5-fluorouracil and low-dose leucovorin in cisplatin-refractory advanced ovarian carcinoma. Gynecol Oncol. 1994;54:180–3.CrossRef Long HJ 3rd, Nelimark RA, Su JQ, Garneau SC, Levitt R, Goldberg RM, et al. Phase II evaluation of 5-fluorouracil and low-dose leucovorin in cisplatin-refractory advanced ovarian carcinoma. Gynecol Oncol. 1994;54:180–3.CrossRef
15.
go back to reference Raymond E, Buquet-Fagot C, Djelloul S, Mester J, Cvitkovic E, Allain P, et al. Antitumor activity of oxaliplatin in combination with 5-fluorouracil and the thymidylate synthase inhibitor AG337 in human colon, breast and ovarian cancers. Anti-Cancer Drugs. 1997;8:876–85.CrossRef Raymond E, Buquet-Fagot C, Djelloul S, Mester J, Cvitkovic E, Allain P, et al. Antitumor activity of oxaliplatin in combination with 5-fluorouracil and the thymidylate synthase inhibitor AG337 in human colon, breast and ovarian cancers. Anti-Cancer Drugs. 1997;8:876–85.CrossRef
16.
go back to reference Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 2004;22:23–30.CrossRef Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 2004;22:23–30.CrossRef
17.
go back to reference Pectasides D, Pectasides M, Farmakis D, Bountouroglou N, Nikolaou M, Koumpou M, et al. Oxaliplatin plus high-dose leucovorin and 5- fluorouracil in pretreated advanced breast cancer: a phase II study. Ann Oncol. 2003;14:537–42.CrossRef Pectasides D, Pectasides M, Farmakis D, Bountouroglou N, Nikolaou M, Koumpou M, et al. Oxaliplatin plus high-dose leucovorin and 5- fluorouracil in pretreated advanced breast cancer: a phase II study. Ann Oncol. 2003;14:537–42.CrossRef
18.
go back to reference Kim YS, Hong J, Sym SJ, Park SH, Park J, Cho EK, et al. Oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX-4) combination chemotherapy as a salvage treatment in advanced gastric cancer. Cancer Res Treat. 2010;42:24–9.CrossRef Kim YS, Hong J, Sym SJ, Park SH, Park J, Cho EK, et al. Oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX-4) combination chemotherapy as a salvage treatment in advanced gastric cancer. Cancer Res Treat. 2010;42:24–9.CrossRef
19.
go back to reference Sundar S, Symonds RP, Decatris MP, Kumar DM, Osman A, Vasanthan S, et al. Phase II trial of oxaliplatin and 5-fluorouracil/leucovorin combination in epithelial ovarian carcinoma relapsing within 2 years of platinum-based therapy. Gynecol Oncol. 2004;94:502–8.CrossRef Sundar S, Symonds RP, Decatris MP, Kumar DM, Osman A, Vasanthan S, et al. Phase II trial of oxaliplatin and 5-fluorouracil/leucovorin combination in epithelial ovarian carcinoma relapsing within 2 years of platinum-based therapy. Gynecol Oncol. 2004;94:502–8.CrossRef
20.
go back to reference Pectasides D, Pectasides M, Farmakis D, Gaglia A, Koumarianou A, Nikolaou M, et al. Oxaliplatin plus high-dose leucovorin and 5-fluorouracil (FOLFOX 4) in platinum-resistant and taxane-pretreated ovarian cancer: a phase II study. Gynecol Oncol. 2004;95:165–72.CrossRef Pectasides D, Pectasides M, Farmakis D, Gaglia A, Koumarianou A, Nikolaou M, et al. Oxaliplatin plus high-dose leucovorin and 5-fluorouracil (FOLFOX 4) in platinum-resistant and taxane-pretreated ovarian cancer: a phase II study. Gynecol Oncol. 2004;95:165–72.CrossRef
21.
go back to reference Rosa DD, Awada A, Mano MS, Selleslags J, Lebrun F, Gil T, et al. Oxaliplatin/5fluorouracil-based chemotherapy was active and well tolerated in heavily pretreated patients with ovarian carcinoma. Arch Gynecol Obstet. 2008;278:457–62.CrossRef Rosa DD, Awada A, Mano MS, Selleslags J, Lebrun F, Gil T, et al. Oxaliplatin/5fluorouracil-based chemotherapy was active and well tolerated in heavily pretreated patients with ovarian carcinoma. Arch Gynecol Obstet. 2008;278:457–62.CrossRef
22.
go back to reference Lee HJ, Kim HS, Park NH, Chung HH, Kim JW, Song YS. Feasibility of oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX-4) chemotherapy in heavily pretreated patients with recurrent epithelial ovarian cancer. Cancer Res Treat. 2013;45:40–7.CrossRef Lee HJ, Kim HS, Park NH, Chung HH, Kim JW, Song YS. Feasibility of oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX-4) chemotherapy in heavily pretreated patients with recurrent epithelial ovarian cancer. Cancer Res Treat. 2013;45:40–7.CrossRef
23.
go back to reference Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;452:228–4.CrossRef Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;452:228–4.CrossRef
24.
go back to reference Rustin GJ, Vergote I, Eisenhauer E, Pujade-Lauraine E, Quinn M, Thigpen T, et al. Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the gynecological Cancer Intergroup (GCIG). Int J Gynecol Cancer. 2011;21:419–23.CrossRef Rustin GJ, Vergote I, Eisenhauer E, Pujade-Lauraine E, Quinn M, Thigpen T, et al. Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the gynecological Cancer Intergroup (GCIG). Int J Gynecol Cancer. 2011;21:419–23.CrossRef
26.
go back to reference Conteduca V, Kopf B, Burgio SL, Bianchi E, Amadori D, De Giorgi U. The emerging role of anti-angiogenic therapy in ovarian cancer (review). Int J Oncol. 2014;44:1417–24.CrossRef Conteduca V, Kopf B, Burgio SL, Bianchi E, Amadori D, De Giorgi U. The emerging role of anti-angiogenic therapy in ovarian cancer (review). Int J Oncol. 2014;44:1417–24.CrossRef
27.
go back to reference Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474:609–15.CrossRef Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474:609–15.CrossRef
28.
go back to reference Hoeijmakers JH. DNA damage, aging, and cancer. N Engl J Med. 2009;361:1475–85.CrossRef Hoeijmakers JH. DNA damage, aging, and cancer. N Engl J Med. 2009;361:1475–85.CrossRef
29.
go back to reference Zhu Y, Zhou S, Liu Y, Zhai L, Sun X. Prognostic value of systemic inflammatory markers in ovarian Cancer: a PRISMA-compliant meta-analysis and systematic review. BMC Cancer. 2018;18(1):443.CrossRef Zhu Y, Zhou S, Liu Y, Zhai L, Sun X. Prognostic value of systemic inflammatory markers in ovarian Cancer: a PRISMA-compliant meta-analysis and systematic review. BMC Cancer. 2018;18(1):443.CrossRef
30.
go back to reference Peng LH, Chen XY, Wu TX. Topotecan for ovarian cancer. Cochrane Database Syst Rev. 2008;2:CD005589. Peng LH, Chen XY, Wu TX. Topotecan for ovarian cancer. Cochrane Database Syst Rev. 2008;2:CD005589.
Metadata
Title
Oxaliplatin plus leucovorin and 5-fluorouracil (FOLFOX-4) as a salvage chemotherapy in heavily-pretreated platinum-resistant ovarian cancer
Authors
Vincenza Conteduca
Giorgia Gurioli
Lorena Rossi
Emanuela Scarpi
Cristian Lolli
Giuseppe Schepisi
Alberto Farolfi
Delia De Lisi
Valentina Gallà
Salvatore Luca Burgio
Cecilia Menna
Andrea Amadori
Lorena Losi
Dino Amadori
Maria Paola Costi
Ugo De Giorgi
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-5180-1

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