Cancer Treatment Today » Ovarian Cancer

Topotecan and Avastin for ovarian cancer – pro

M Levin, MD — Thu, 22 Nov 2012 18:46:49 +0000

Topotecan is a water-soluble, semisynthetic analogueof camptothecin that inhibits the nuclear enzyme topoisomeraseI. Topotecan has been approved by the U.S. Food and DrugAdministration (FDA) for the treatment of recurrent epithelialovarian cancer and relapsed small cell lung cancer,and has also demonstrated activity in hematologic malignancies and solid tumors including non-small cell lung, cervical, and colon cancers. In ovariancancer, topotecan has demonstrated activity in both platinum-and paclitaxel-resistant tumors, with response rates rangingfrom 12%-33%. In a randomized, phase III study,ovarian cancer patients showed similar response rates with topotecan(21%; n = 112) and paclitaxel (13%; n = 114; p = 0.138) Approximately half of all patients in both arms of thestudy had progressed on a platinum-based regimen or had relapsedwithin 6 months of completing first-line therapy. Topotecanproduced responses in 8 of 61 (13%) patients in whom paclitaxelhad failed to produce a response. Similarly, paclitaxel producedresponses in 5 of 49 (10%) patients in whom topotecan had failedto produce a response. That phase III study, and earlierphase II studies, established topotecan as an important treatment option for patients with either platinum-sensitive or platinum-refractoryrelapsed ovarian cancer. NCCN lists it as well as level 2b recommendation. It is generally assumed that fallopian tube adenocarcinoma is of ovarian tissue origin and should be treated as ovarian cancer.

NCCN supports second line use of Avastin alone or in combination – on p. OV-D, 1.

In terms of putting the two drugs together, only one recently completed study addresses this question. Patients (N = 40) received a median of 8 treatment cycles. Toxicity was generally mild or moderate, with neutropenia (18%), hypertension (20%), gastrointestinal toxicity (18%), pain (13%), metabolic toxicity (15%), bowel obstruction (10%), and cardiotoxicity (8%) being the most common grade 3 and 4 adverse events. No bowel perforations, febrile neutropenia, or treatment-related deaths occurred. Median PFS and OS were 7.8 (95% confidence interval [CI], 3.0-9.4) and 16.6 months (95% CI, 12.8-22.9), with 22 (55%) patients progression-free for ≥6 months. Ten (25%) patients had partial response (PR), 14 (35%) had stable disease (SD), and 16 (40%) had PD. Patients treated with 2 prior regimens received greater benefit than patients treated with 1: PR/SD, 78.9% versus 42.9% (P = .03); median PFS, 10.9 versus 2.8 months (P = .08); median OS, 22.9 versus 12.8 months (P = .02).

It concluded that a weekly topotecan and biweekly bevacizumab combination demonstrates acceptable toxicity and encouraging efficacy in patients with platinum-resistant OC; further study is warranted.

McGonigle KF, Muntz HG, Vuky J, Paley PJ, Veljovich DS, Greer BE, Goff BA, Gray HJ, Malpass Combined weekly topotecan and biweekly bevacizumab in women with platinum-resistant ovarian, peritoneal, or fallopian tube cancer: results of a phase 2 study. Cancer. 2011 Aug 15;117(16):3731-40.

Miller DS, Blessing JA, Lentz SS et al. Phase II evaluation of three-day topotecan in recurrent platinum-sensitive ovarian or primary peritoneal cancer: a Gynecologic Oncology Group study. Presented at the 33rd Annual Meeting of the Society of Gynecologic Oncologists, Miami, FL, March 16–20, 2002.

Burger RA, Brady MF, Bookman MA, et al. Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): A Gynecologic Oncology Group study. J Clin Oncol. 2010;28:abstract LBA1, ASCO Annual Meeting Proceedings (Post-Meeting Edition). Available at: http://meeting.ascopubs.org/cgi/content/abstract/28/18_suppl/LBA1

Monk B, Han E, Josephs-Cowan C, et al. Salvage Bevacizumab (rhuMAB VEGF)-based Therapy after Multiple Prior Cytotoxic Regimens in Advanced Refractory Epithelial Ovarian Cancer. Gynecologic Oncology. 2006; 102: 140-144.

Robert A. Burger, Experience With Bevacizumab in the Management of Epithelial Ovarian Cancer, Journal of Clinical Oncology, Vol 25, No 20 (July 10), 2007: pp. 2902-2908

Burger R, Brady MF, Bookman MA, et al: Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): A Gynecologic Oncology Group study. 2010 ASCO Annual Meeting. Abstract LBA1. Presented June 6, 2010.

For Lay version see here

Topotecan for ovarian cancer – pro

M Levin, MD — Tue, 04 Sep 2012 13:02:17 +0000

Topotecan is a water-soluble, semisynthetic analogueof camptothecin that inhibits the nuclear enzyme topoisomeraseI. Topotecan has been approved by the U.S. Food and DrugAdministration (FDA) for the treatment of recurrent epithelialovarian cancer and relapsed small cell lung cancer,and has also demonstrated activity in hematologic malignancies and solid tumors including non-small cell lung, cervical, and colon cancers. It is no longer experimental.
In ovariancancer, topotecan has demonstrated activity in both platinum-and paclitaxel-resistant tumors, with response rates rangingfrom 12%-33%. In a randomized, phase III study,ovarian cancer patients showed similar response rates with topotecan(21%; n = 112) and paclitaxel (13%; n = 114; p = 0.138) Approximately half of all patients in both arms of thestudy had progressed on a platinum-based regimen or had relapsedwithin 6 months of completing first-line therapy. Topotecan produced responses in 8 of 61 (13%) patients in whom paclitaxelhad failed to produce a response. Similarly, paclitaxel producedresponses in 5 of 49 (10%) patients in whom topotecan had failedto produce a response. That phase III study, and earlierphase II studies, established topotecan as an important treatment option for patients with either platinum-sensitive or platinum-refractoryrelapsed ovarian cancer. NCCN lists it as well as level 2b recommendation.It is generally assumed that primary peritoneal serous adenocarcinoma is of ovarian tissue origin and should be treated as ovarian cancer.

Bookman MA, Malmstrom H, Bolis G et al. Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel. J Clin Oncol 1998;16:3345–3352.

nccn.org, ovarian

Intraperitoneal chemotherapy for ovarian cancer – pro

admin — Mon, 03 Sep 2012 00:42:52 +0000

Lay Summary: IP Chemotherapy is now standard for ovarian cancer.

The recommended treatment for ovarian cancer entails primary surgery for diagnosis, staging and cytoreduction (the removal of cancerous mass), followed by chemotherapy. Recommended initial chemotherapy is generally a platinum-and-taxane chemotherapy combination.Intravenous (IV) administration of chemotherapy drugs is done by inserting a needle into a vein in the body of a patient whereas intraperitoneal (IP) administration of chemotherapy is done through a surgically implanted catheter that allows passage of fluids into the abdomen of a woman.
According to a study published in the New England Journal of Medicine, patients who received part of their chemotherapy via an IP route had a median survival time of 16 months longer than women who received IV chemotherapy. Certain chemotherapy drugs, such as cisplastin and paclitaxel have been found to have distinct advantages when given via the IP route. These advantages include higher drug concentrations and longer drug half lives (meaning the drug will remain active for a longer period of time) in the peritoneal cavity. It does require inpateint stays, although homecare companies are beginning to provide this service at home. It is, however, not universally available or adopted because it is cumbersome. Where paclitaxel cannot be used, cytoxan is a easonable alternative, supported by phase II studies as well as phase III comparative studies of IV cytoxan/cisplatin versus paclitaxel/ cisplatin.

Elit L, Oliver TK, Covens A, et al. Intraperitoneal chemotherapy in the first-line treatment of women with Stage III epithelial ovarian cancer: a systematic review with meta-analysis. Cancer. 2007;109:692-702.

Armstrong D, Bundy B, Wenzel L, et al. Intraperitoneal Cisplatin and Paclitaxel in Ovarian Cancer. New England Journal of Medicine. 2005; 354:34-43

nccn.org, ovarian

Maurie Markman, MD Second-line chemotherapy for refractory cancer: Intraperitoneal chemotherapy Seminars in Surgical Oncology Volume 10, Issue 4 , Pages 299 – 304, 2006

Ovarian Cancer/Abraxane – pro

M Levin, MD — Mon, 03 Sep 2012 00:41:47 +0000

Paclitaxel is one of the most active agents in the treatment of ovarian carcinoma. Novel agents such as abraxane are solvent free and currently being evaluated to potentially avoid certain patient side effects. Abraxane is an albumin-stabilised nanoparticle formulation of paclitaxel designed to overcome various insolubility problems encountered with paclitaxel. This nano-technology eliminates the need for toxic solvents like cremophor, which limits the dose of paclitaxel that can be administered and hence affect overall drug efficacy. Cremophor is also know to cause various types of allergic reactions in patients who receive paclitaxel. Albumin receptor-mediated paclitaxel-transport mechanism is analogous to the opening of a ‘trapdoor’ on the endothelial cell wall within blood vessels. This facilitates easy passage of abraxane from the bloodstream via the blood vessels to the underlying tumour tissue. A study showed that Abraxane causes few allergic reactions in ovarian cancer patients. More recently, two studies were presented at the 43rd Annual Meeting of the American Society of Clinical Oncology (ASCO) held June 2 – 5, 2007 in Chicago. The first study titled “An open-label, Phase II trial of nab-paclitaxel, carboplatin and bevacizumab in first-line patients with advanced non-squamous non-small cell lung cancer (NSCLC)” (Abstract number 7610) was a randomized, open-label Phase II of nab-paclitaxel dosed every three weeks in combination with carboplatin and bevacizumab in 50 patients with advanced non-squamous NSCLC. The primary end point of the study was response rate based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The other study titled “Results of a Phase II evaluation of nab-paclitaxel in platinum-sensitive patients with recurrent ovarian, peritoneal or fallopian tube cancer” (Abstract number 5525) was an open level Phase II study to evaluate single agent nab- paclitaxel in a platinum-sensitive patient population. Both studies demonstrated ABRAXANE’s activity and tolerability as a single agent for ovarian cancer. No phase III studies have yet been iniitated as per clinicaltrials.gov. As such, it has not been demonstrated to be as effective as established alternatives. There are no studies in resistant or multiply treated patients.

NCCN does recommend it for salvage therapy but the most recent Alberta guideline does not.

Micha JP, ET AL, Abraxane in the treatment of ovarian cancer: the absence of hypersensitivity reactions. : Gynecol Oncol. 2006 Feb;100(2):437-8. Epub 2005 Oct

Abraxane, Prescribing information

NCCN.ORG, Ovarian Cancer 2912

Alberta Provincial Gynecologic Oncology Tumour Team. Epithelial ovarian, fallopian tube, and primary peritoneal cancer. Edmonton (Alberta): Alberta Health Services, Cancer Care; 2010 Jul. 19 p. (Clinical practice guideline; no. GYNE-005). [104 references]

PET for Ovarian cancer – pro

admin — Mon, 03 Sep 2012 00:41:47 +0000

The test is investigational, in the sense that experts agree that it needs to be better studied for staging, reataging and surveillacne of ovarian cancer, but it is not routinely recommended by guidelines. Many studies suggest that PET is a more sensitive modality than CT . However, the most recent guideline by Prefontainee et al in 2010 says: “PET is not recommended for staging of ovarian cancer.” It comes to the same conclusion for its use for recurrence. PET is not recommended for detecting recurrence or restaging patients not being considered for surgery. A recommendation cannot be made for or against the use of PET for patients being considered for secondary cytoreduction because of insufficient evidence.” 1

For evaluating possible recurrences, PET is graded 7/9 by AACR. CAT is 9. It states that if available PET can substitute for CT (but not that it is preferred or better). 2

NCCN only recommends it for initital staging if CT or MRI is indeterminate.

For evaluating possible recurrences, PET is graded 7/9 by AACR’CAT is 9. It states that if available PET can substitute for CT (but not that it is preferred or better). However, in the situation of rising CA-125 levels, PET is more accepted. NCCN lists PET in this situation as a Grade 2b recommendation.

1.Prefontaine M, Walker-Dilks C. PET imaging in ovarian cancer: recommendations. Toronto (ON): Cancer Care Ontario (CCO); 2009 Jan 19. 17 p. (Recommendation report – PET; no. 7). [46 references]

2.Agency for Healthcare Research and Quality (AHRQ). Positron emission tomography for nine cancers (bladder, brain, cervical, kidney, ovarian, pancreatic, prostate, small cell lung, testicular). Prepared by the University of Alberta Evidence-Based Practice Center for the Agency for Healthcare Research and Quality (AHRQ). Rockville, MD: AHRQ; 2008.

3.Javitt MC, Fleischer AC, Andreotti RF, Angtuaco TL, Horrow MM, Lee SI, Lev-Toaff AS, Scoutt LM, Zelop C, Expert Panel on Women’s Imaging. Staging and follow-up of ovarian cancer. [online publication]. Reston (VA): American College of Radiology (ACR); 2007. 5 p. [38 references]

4. NCCN, OV-1, 2015

Risum S, Hogdall C, Loft A, et al. The diagnostic value of PET/CT for primary ovarian cancer – A prospective study. Gynecol Oncol 2007;105:145-9.

Maurie Markman Use of Positron Emission Tomography Scans in Ovarian Cancer: A Diagnostic Technique in Search of an Indication Journal of Clinical Oncology, Vol 23, No 30 (October 20), 2005: pp. 7385-7387

Norbert Avril, Stefanie Sassen, Barbara Schmalfeldt, Joerg Naehrig, Stephan Rutke, Wolfgang A. Weber, Martin Werner, Henner Graeff, Markus Schwaiger, and Walther Kuhn Prediction of Response to Neoadjuvant Chemotherapy by Sequential F-18-Fluorodeoxyglucose Positron Emission Tomography in Patients With Advanced-Stage Ovarian Cancer JCO 2005 23: 7445-7453

Y. Hama, Positron emission tomography with 18F-fluoro-2-deoxyglucose for the detection of recurrent ovarian cancer. Int J Clin Oncol. 2006 Jun;11(3):250-1.

Rusu Daniela, Carlier Thomas, Colombié Mathilde, Goulon Dorothée, Fleury Vincent, Rousseau Nicolas, Berton-Rigaud Dominique, Jaffre Isabelle, Kraeber-Bodéré Françoise, Campion Loic, Rousseau Caroline linical and Survival Impact of FDG PET in Patients with Suspicion of Recurrent Ovarian Cancer: A 6-Year Follow-Up rontiers in Medicine VOLUME=2 YEAR=2015 p. 46

Avastin for Ovarian Cancer: Relapsed and refractory – pro

M Levin, MD — Mon, 03 Sep 2012 00:40:11 +0000

Lay Summary: Avastin appears to add to combination chemotherapies for ovarian cancer.

Patients with ovarian cancer that has recurred or progressed following prior therapies, have unfavorable long-term outcomes with standard therapies. Although additional chemotherapy can be used to treat these patients, they often have minimal anti-cancer responses as well as side effects from treatment. Initial study of Avastin focused on this unfavourable group. Researchers from California conducted a study to evaluate the effectiveness of Avastin for the treatment of recurrent ovarian cancer. This trial included 33 patients who had received extensive prior chemotherapy. The majority of patients were treated with Avastin as a single agent. This is the 3rd positive phase II trial. The previous trials included Avastin with metronomic cyclophosphamide and one with a taxane. A phase III trial, however, was stopped by Genetech when an unexpected 11% of participants developed bowel perforations. The debate about why this happened and how it was related to the patient characteristics still has not been resolved.

Patients with ovarian cancer that has recurred or progressed following prior therapies, have unfavorable long-term outcomes with standard therapies. Although additional chemotherapy can be used to treat these patients, they often have minimal anti-cancer responses as well as side effects from treatment. Initial study of Avastin focused on this unfavourable group. Researchers from California conducted a study to evaluate the effectiveness of Avastin for treatment of recurrent ovarian cancer. This trial included 33 patients who had received extensive prior chemotherapy. The majority of patients were treated with Avastin as a single agent. This is the 3rd positive phase II trial. The previous trials included Avastin with metronomic cyclophosphamide and one with a taxane. A phase III trial, however, was stopped by Genetech when an unexpected 11% of participants developed bowel perforations. The debate about why this happened and how it was related to the patient characteristics still has not been resolved. Nevertheless, based on the existing evidence, NCCN has now added Avastin to its list of recommended drugs for ovarian cancer.

NCCN supports second line use of Avastin alone or in combination , but the only combination that it mentions specifically is gemcitabine/carboplatin/bevacizumab and carboplatin liposomal doxorubicin with or without Avastin. The discussion of the guidelines at MS-14 (makes it clear that this is the correct interpretation of teh OV-E page. Carboplatin plus gemcitabine with or without bevacizumab has recently been published as the OCEANS trial (Aghajanian et al). This study showed a higher response rate and a slightly prolonged time to recurrence with the addition of bevacizumab. However, overall survival was identical. Therefore, this regimen has received only a category 2B level of evidence in NCCN guidelines.

Perren T, Swart AM, Pfisterer J, et al: ICON7: A phase III randomized gynaecologic cancer intergroup trial of concurrent bevacizumab and chemotherapy followed by maintenance bevacizumab versus chemotherapy alone in women with newly diagnosed epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer. Program and abstracts of the 35th European Society for Medical Oncology (ESMO) Congress; October 8-12, 2010; Milan, Italy. Abstract LBA4.

Bidus MA, Webb JC, Seidman JD, et al. Sustained response to bevacizumab in refractory well-differentiated ovarian neoplasms.Gynecologic Oncology. 2006;May 11

Cohn DE, Valmadre S, Resnick KE, et al. Bevacizumab and weekly taxane chemotherapy demonstrates activity in refractory ovarian cancer. Gynecologic Oncology. 2006;March 7

Robert A. Burger, Experience With Bevacizumab in the Management of Epithelial Ovarian Cancer, Journal of Clinical Oncology, Vol 25, No 20 (July 10), 2007: pp. 2902-2908

Cohn DE, Valmadre S, Resnick KE, et al. Bevacizumab and weekly taxane chemotherapy demonstrates activity in refractory ovarian cancer. Gynecologic Oncology. 2006;March

Daniela Luvero et al, Treatment options in recurrent ovarian cancer: latest evidence and clinical potential. Ther Adv Med Oncol. 2014 Sep; 6(5): 229239 7;

NCCN Ovarian Cancer OV-C, 6 of 8, 2019

Adjuvant chemotherapy for stage I ovarian cancer – pro

admin — Mon, 03 Sep 2012 00:35:55 +0000

The stage of ovarian cancer is an important prognostic factor that influences survival and the choice of therapy. The quality of the surgical staging is a key determinant of treatment recommendations. Women who have undergone optimal surgical staging, including pelvic and para-aortic lymph node sampling, and have stage I disease may or may not benefit from adjuvant platinum-based chemotherapy. The results of the largest trial comparing adjuvant chemotherapy to no chemotherapy in women with early stage ovarian cancer (International Collaborative Ovarian Neoplasm Study/Adjuvant ChemoTherapy In Ovarian Neoplasm [ICON/ACTION] Trial) are controversial because:
A subgroup analysis of the ACTION Trial showed no benefit from adjuvant chemotherapy in women who underwent optimal surgical staging, but that analysis was underpowered.
The entry criteria for the ICON Trial were vague and did not reflect the standard of surgical care generally offered. The meta-analysis demonstrates that stage I patients have an improved outcome with adjuvant chemotherapy. However, an estimated 90% of women undergoing surgical resection for ovarian cancer do not undergo optimal surgical staging. If the restaging of a suboptimally staged patient reveals a more advanced disease, chemotherapy is the preferred treatment option. If reoperation confirms stage I disease, there is insufficient evidence for or against adjuvant chemotherapy. However,
NCCN lists adjuvant chemotherapy or observation alone as an option for stage Ia ovarian cancer. The most established regimen is Taxol and carboplatin.

http://www.nccn.org/professionals/physician_gls/PDF/ovarian.pdf, p.7

Gynecology Cancer Disease Site Group. Elit L, Fyles A, Chambers A, Fung Kee Fung M, Covens A, Carey M. Adjuvant care for stage I ovarian cancer [full report]. Toronto (ON): Cancer Care Ontario (CCO); 2004 May 3. 33 p. (Practice guideline report; no. 4-13). [62 references]

Intraperitoneal interferon – pro

admin — Mon, 03 Sep 2012 00:34:29 +0000

Intraperitoneal instillation of interferon has been investigated mostly in ovarian cancer, but also in ascites and pleural effusion of other casues, including colorectal cancer. This is distinct from anti-tumor effects in colon cancer, for which NCCN specifically does not recommed interferon.The effect on the effusion may or may not be related to direct anticancer effect. Unfortunately, none of the studies included sufficient numbers of patients to be able to make a recomendation for this therapy. One study found that: “At the dose of 10 M units/m2 of intraperitoneal -2B-IFN, this regimen did not appear to produce clinically significant palliation of the ascites in most patients.”

Berek J.S.; Markman M.; Stonebraker B.; Lentz S.S.; Adelson M.D.; DeGeest K.; Moore D.Intraperitoneal Interferon- in Residual Ovarian Carcinoma: A Phase II Gynecologic Oncology Group Study Gynecologic Oncology, Volume 75, Number 1, October 1999 , pp. 10-14(5)

Gavin C. E. Stuart, M.D.Intraperitoneal interferon in the management of malignant ascites
Cancer Cytopathology Volume 71 Issue 6, Pages 2027 – 2030

R. S. Freedman, A. P. Kudelka, J. J. Kavanagh, C. Verschraegen, C. L. Edwards, M. Nash, L. Levy, E. N. Atkinson, H.-Z. Zhang, B. Melichar, et al.
Clinical and Biological Effects of Intraperitoneal Injections of Recombinant Interferon-{{gamma}} and Recombinant Interleukin 2 with or without Tumor-infiltrating Lymphocytes in Patients with Ovarian or Peritoneal Carcinoma
Clin. Cancer Res., June 1, 2000; 6(6): 2268 – 2278.

Taxol and Carboplatin for Ovarian cancer – pro

admin — Mon, 03 Sep 2012 00:33:33 +0000

The combination of paclitaxel and carboplatin in a three weeks schedule has emerged as the current standard approach for the adjuvant treatment of ovarian cancer.After numerous phase I/II trials of carboplatin and paclitaxel combinations, three large randomized phase III trials were performed comparing cisplatin-paclitaxel with carboplatin-paclitaxel. All three trials demonstrated equivalence with respect to median progression-free survival for carboplatin-paclitaxel and cisplatin-paclitaxel. Data are not mature enough to comment on overall survival. As anticipated, carboplatin-paclitaxel was better tolerated and more convenient, and has since replaced the cisplatin-paclitaxel combination as the preferred regimen for first-line therapy.

It is FDA approved. Initially Taxol was approved with cisplatin, as follows: “Taxol is indicated as first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary. As first-line therapy, TAXOL is indicated in combination with cisplatin.” Then FDA approved carbopaltin, as follows: ” PARAPLATIN (carboplatin aqueous solution) INJECTION is indicated for the initial treatment of advanced ovarian carcinoma in established combination with other approved chemotherapeutic agents.”

In regard to weekly Taxol, weekly schedule of carbotaxol chemotherapy in the treatment of advanced ovarian cancer is both well tolerated and efficacious. however, evidence for this is phase II at this time.

Neijt JP, Hansen M, Hansen SW, et al. Randomised phase III study in previously untreated epithelial ovarian cancer FIGO stage IIB, IIC, III, IV comparing paclitaxel-cisplatin and paclitaxel-carboplatin [Abstract 1259]. Proc ASCO 1997; 16:352.

Ozols RF, Bundy BN, Fowler J, et al. Randomised phase III study of cisplatin (CIS)/paclitaxel (PAC) versus carboplatin (CARBO)/PAC in optimal stage III epithelial ovarian cancer (OC): A Gynaecologic Oncology Study Group Trial (GOG 158) Proc ASCO. 18:356. [Abstract 1373].

Jalid Sehouliet al, First-Line Chemotherapy with Weekly Paclitaxel and Carboplatin for Advanced Ovarian Cancer: A Phase I Study Gynecologic Oncology Volume 85, Issue 2, May 2002, Pages 321-326

SEHOULI J et al, Weekly taxol (T) and carboplatin (P) as first-line therapy in advanced ovarian cancer (AOC): overall survival data of a phase ii-study in 130 patients Acta Obstetrica et Gynaecologica Japonica 57(2), 784,2005

Gemcitabine carboplatin for ovarian cancer – pro

admin — Sun, 02 Sep 2012 17:26:11 +0000

Gemcitabine and carboplatin are not FDa approved in combination for ovarian cancer; however, the combination is supported by randomized clinical trials. Carboplatin is FDA approved in other combinations. The combination is experimental because it is not FDA approved, but medically necessary. Many patients with advanced ovarian cancer will develop recurrent disease. For those patients who have recurrence of disease at least 6 months after initial therapy, the paclitaxel-platinum combination has been shown to be a superior treatment to platinum monotherapy. However, many patients develop clinically relevant neurotoxicity, frequently resulting in treatment discontinuation. The efficacy and safety of an alternative regimen that does not show significant neurotoxicity were evaluated by comparing gemcitabine-carboplatin with carboplatin in platinum-sensitive recurrent ovarian cancer patients in a Gynecologic Cancer InterGroup trial of the Arbeitsgemeinschaft Gynakologische Onkologie Ovarian Cancer Study Group, the National Cancer Institute of Canada Clinical Trials Group, and the European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group. Gemcitabine-carboplatin treatment significantly improves the PFS of patients with platinum-sensitive recurrent ovarian cancer. These results were confirmed in 2006. NCCN lists this combination for recurrent disease on p.22.

Pfisterer J, Vergote I, Du Bois A, Eisenhauer E; AGO-OVAR,; NCIC CTG; EORTC GCG. Combination therapy with gemcitabine and carboplatin in recurrent ovarian cancer.Int J Gynecol Cancer. 2005 May-Jun;15 Suppl 1:36-41.

Pfisterer J, Plante M, Vergote I, du Bois A, Hirte H, Lacave AJ, Wagner U, Stähle A, Stuart G, Kimmig R, Olbricht S, Le T, Emerich J, Kuhn W, Bentley J, Jackisch C, Lück HJ, Rochon J, Zimmermann AH, Eisenhauer E; AGO-OVAR; NCIC CTG; EORTC GCG. Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG.
J Clin Oncol. 2006 Oct 10;24(29):4699-707.

NCCN.ORG, Ovarian p.10