Clinical evidence for topotecan-paclitaxel non--cross-resistance in ovarian cancer.
OBJECTIVE
A large, randomized study comparing the efficacy and safety of topotecan versus paclitaxel in patients with relapsed epithelial ovarian cancer showed that these two compounds have similar activity. In this study, a number of patients crossed over to the alternative drug as third-line therapy, ie, from paclitaxel to topotecan and vice versa. We therefore were able to assess the degree of non-cross-resistance between these two compounds.


METHODS
Patients who had progressed after one platinum-based regimen were randomized to either topotecan (1.5 mg/m(2)/d) x 5 every 21 days (n = 112) or paclitaxel (175 mg/m(2) over 3 hours) every 21 days (n = 114). A total of 110 patients received cross-over therapy with the alternative drug (61 topotecan, 49 paclitaxel) as third-line therapy.


RESULTS
Response rates to third-line cross-over therapy were 13.1% (8 of 61 topotecan) and 10.2% (5 of 49 paclitaxel; P =.638). Seven patients who responded to third-line topotecan and four patients who responded to paclitaxel had failed to respond to their second-line treatment. Median time to progression (from the start of third-line therapy) was 9 weeks in both groups, and median survival was 40 and 48 weeks for patients who were receiving topotecan or paclitaxel, respectively. The principal toxicity was myelosuppression; grade 4 neutropenia was more frequent with topotecan (81.4% of patients) than with paclitaxel (22.9% of patients).


CONCLUSIONS
Topotecan and paclitaxel have similar activity as second-line therapies with regard to response rates and progression-free and overall survival. We demonstrated that the two drugs have a degree of non-cross-resistance. Thus, there is a good rationale for incorporating these drugs into future first-line regimens.
Royal Marsden Hospital, London, UK. Martin.Gore@rmh.nthames.nhs.uk
M
M
Gore
W
W
ten Bokkel Huinink
J
J
Carmichael
A
A
Gordon
N
N
Davidson
R
R
Coleman
M
M
Spaczynski
J F
JF
Héron
G
G
Bolis
H
H
Malmström
J
J
Malfetano
C
C
Scarabelli
P
P
Vennin
G
G
Ross
S Z
SZ
Fields
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018592:Cross-Over Studies; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000401:mortality; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D017239:Paclitaxel / Q000494:pharmacology*; D016016:Proportional Hazards Models; D015996:Survival Rate; D019772:Topotecan / Q000494:pharmacology*; D014481:United States / Q000453:epidemiology
D000970:Antineoplastic Agents; D019772:Topotecan; D017239:Paclitaxel