Cancer Treatment Today

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.”

This indication does not exclude neoadjuvant use. However, overall, treated with this approach likely have an inferior outcome to patients undergoing initial maximal cytoreductive surgery followed by chemotherapy. The current opinon is that primarys urgery should always be attemtped, if possible. Patients with advanced ovarian cancer who are not candidates for surgical cytoreduction may be treated initially with 2-3 cycles of conventional chemotherapy and can then be reevaluated for surgical cytoreduction. However, optimal initial cytoreduction remains the standard of care for most patients. There is evidence(Vergote et al) that neoadjuvant chemotherapy followed by interval surgery provided equivalent outcomes to standard primary surgery followed by chemotherapy in women with stage III and IV ovarian cancer. There is no evidence that it is a superior approach.

According to the 2011 NCCN ovarian cancer guidelines, a patient should be evaluated for neoadjuvant chemotherapy by a fellowship-trained gynecologist oncologist before being considered a nonsurgical candidate. In its discussion, NCCN points out several criticisms of the Vergote study.

Vergote I, Tropé CG, Amant F, Kristensen GB, Ehlen T, Johnson N, et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. Sep 2 2010;363(10):943-53.

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

nccn.org, ovarain cancer, MS-5