The evidence supporting the use of this protocol comes from an open label, randomised, phase III trial reported by Pfisterer et al.r From September 1999 to April 2002, a total of 356 patients with platinum-sensitive recurrent ovarian cancer were randomised to receive gemcitabine (1000 mg/m2 day 1 and day 8 plus carboplatin AUC=4 day 1 (n=178) or carboplatin AUC =5 day 1 (n=178) every 21 days.
The primary end point was progression-free survival and secondary end points were response rate, duration of response, overall survival, quality of life, and toxicity.r
Efficacy
After a median follow-up of 17 months, median PFS was 8.6 months for gemcitabine plus carboplatin and 5.8 months for carboplatin. The hazard ratio for PFS was 0.72 (p=0.0031). Response rate was 47.2% for gemcitabine plus carboplatin and 30.9% for carboplatin (p=0.0016). The HR for overall survival was 0.96 (p=0.7349).r
Kaplan-Meier estimates of progression-free survivalr
© Journal of Clinical Oncology 2006
Kaplan-Meier estimates of overall survivalr
© Journal of Clinical Oncology 2006
Toxicity
Although myelosuppression was significantly more common in the combination arm, sequelae such as febrile neutropenia or infections were uncommon. There were no statistically significant differences in quality of life scores between both treatment arms.r
Grade 3/4 toxicity r |
GC arm %
(n=175) |
C arm %
(n=174) |
p-value |
Anaemia |
27 |
8 |
<0.001 |
Neutropenia |
71 |
12 |
<0.001 |
Thrombocytopenia |
35 |
11 |
<0.001 |
Hypersensitivity |
2 |
3 |
0.7503 |
Alopecia |
NA |
NA |
NA |
Diarrhoea |
2 |
0 |
0.2479 |
Dyspnoea |
1 |
2 |
0.6848 |
Fatigue |
2 |
2 |
0.99 |
Febrile neutropenia |
1 |
0 |
0.4986 |
Neuropathy (motor) |
0.6 |
0 |
0.99 |
Neuropathy (sensory) |
1 |
2 |
0.6848 |
Vomiting |
3 |
2 |
0.7234 |
GC arm = gemcitabine plus carboplatin; C arm = carboplatin