What is the role of dose-dense therapy?
The introduction of paclitaxel/platinum combination chemotherapy and (interval) debulking surgery has significantly improved the prognosis of patients with ovarian cancer. Yet, many patients die of drug-resistant disease. Second-line chemotherapy may result in prolonged secondary remissions with alleviation of symptoms and improvement of quality of life. The response to second-line chemotherapy is strongly related to platinum sensitivity. More than 60% of platinum-sensitive patients respond to a re-challenge with platinum-containing chemotherapy. In platinum-resistant patients, on the contrary, the response rate to a re-challenge with 3-weekly platinum or any nonplatinum chemotherapy is less than 20%. The response to dose-dense weekly platinum-based regimens ranged from 48% to 64% in platinum-resistant patients. Moreover, the majority of the patients responded within 8 weeks after the start of the treatment. The progression-free survival ranged from a median of 5 months in a study using cisplatin/etoposide, to 11 months in a study with paclitaxel/carboplatin. The median survival was 11-15 months. The outpatient weekly paclitaxel/carboplatin regimen, with paclitaxel at a dose of 90 mg/m(2) and carboplatin at area under the curve 4, seems similarly effective and is better tolerated. Dose-dense weekly paclitaxel/carboplatin is an effective and well-tolerated therapy for platinum-sensitive, as well as platinum-resistant tumors. Responses to therapy are observed within 8 weeks in the majority of the patients. Whether a weekly regimen indeed is more effective than 3-weekly paclitaxel/carboplatin needs to be answered in a randomized study.
van der Burg
M E L
ME
Department of Medical Oncology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
van der Gaast
A
A
Vergote
I
I
Burger
C W
CW
van Doorn
H C
HC
de Wit
R
R
Stoter
G
G
Verweij
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D016190:Carboplatin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D013509:Gynecologic Surgical Procedures; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome
D005047:Etoposide; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin