Carboplatin plus paclitaxel once a week versus every 3 weeks in patients with advanced ovarian cancer (MITO-7):
A randomized, multicentre, open-label, phase 3 trial

Disease site

Ovary

Publication month/year

February, 2014

Study question

To assess whether a weekly schedule of carboplatin plus paclitaxel is more effective than the same drug combination given every 3 weeks

Type of study

Randomised controlled trial (RCT)

Interventions compared

Weekly vs every 3 weeks regimens of Carboplatin plus Paclitaxel

Experimental arm (Intervention)

Weekly Carboplatin plus Paclitaxel

Control arm

Standard Carboplatin plus Paclitaxel every 3 weeks

Primary outcome
  • Quality of Life
  • Progression-free survival
Secondary outcome
  • Overall survival 
  • Toxic effects 
  • The proportion of patients who achieved an objective response
Inclusion criteria
  • Women older than 18 years of age
  • Cytological or histological diagnosis of the epithelial ovarian, fallopian tube, or peritoneal cancer
  • Stage IC – IV disease (Based on FIGO)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 2 or lower 
  • Life Expectancy of at least 3 months
  • Adequate bone marrow, kidney, and liver functions
Exclusion criteria
  • History of clinically relevant heart disease or any disorders that pose contraindications to treatment drugs.
  • Previous or concomitant malignant disease (except non-melanoma skin cancer or in-situ carcinoma of the uterine cervix) 
  • Previous history of chemotherapy
Results:
*No significant difference between groups was found on multivariate analysis. Residual disease and FIGO stage were independent predictors of progression-free survival.
Intervention arm Control arm
Randomised(n) 406 404
Received treatment(n) Weekly Carboplatin plus Paclitaxel Carboplatin plus Paclitaxel every 3 weeks
Progression-free survival 18.3 months
(95% CI 16.8 – 20.9)
17.3 months
(95% CI 15.2 – 20.2)
Quality of Life FACT-O/TOI worsened at week 1 then remained stable for week 4 and 7 FACT-O/TOI scores worsened at every cycle
[Week 1, 4 and 7]
1-year overall survival 77.3% (95% CI 72.8 – 82.1) 78.9% (95% CI 74.3 – 83.8)
Toxic Effects - Grade 3-4 Neutropenia
(167 [42%])
- Febrile Neutropenia
(2 [0.5%])
- Grade 3-4 thrombocytopenia
(4 [1%])
- Grade 2 or worse neuropathy
(24 [6%])
- Grade 3-4 Neutropenia
(200 [50%])
- Febrile Neutropenia
(11 [3%])
- Grade 3-4 thrombocytopenia
(27 [7%])
- Grade 2 or worse neuropathy (68 [17%])
Objective response 95 (56.2% 95% CI 48.4 – 63.8)
had an objective response.
100 (58.8%, 95% CI 51.0–66.3)
had an objective response.
Mortality due to chemotherapy 1 2
Conclusions

The proposed weekly regimen of carboplatin and paclitaxel improves quality of life and has a better toxicity profile yet it does not alter progress-free or overall survival. Despite how challenging it to adhere to and provide such regimen, it is a reasonable alternative first-line treatment for advanced ovarian cancer.

Study limitations

The study’s sample is not representative enough to account for differences in treatment endpoints such as those caused by genetic polymorphism. In addition, the usage of consistent dosing to accurately predict treatment effect might have led to inefficient and ineffective outcomes. 

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