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Weekly chemo offers quality-of-life edge in advanced ovarian cancer

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Regimen may blunt peak effect of carboplatin

The results of this trial can be compared with those of the Japanese Gynecologic Oncology Group (JGOG) trial 3016. That study found that weekly dose-dense paclitaxel (80 mg/m2 per week given for 3 weeks) with every-3-week carboplatin (AUC 6) yielded superior progression-free and overall survival when compared with the standard 3-weekly regimen in women with advanced serous tumors (Lancet 2009;374:1331-8).

The trials had several differences, however. The JGOG trial had a larger share of patients with advanced-stage disease and used a weekly regimen that may have been more dose dense than the one used in MITO-7. Also, Japanese and European patients may differ genetically in ways that affect hepatic metabolism of these chemotherapy agents.

It may be that the MITO trial is just not dose dense enough or not a dose-dense trial because the carboplatin was given weekly, and that may blunt the peak effect, which may be relevant, and the Taxol [paclitaxel] is at a cumulative lower dose. So the pharmacokinetic advantage that we try to get with the peak dose of a platinum agent may have been blunted, and the maximum impact of weekly paclitaxel may have been negated.

It will be important to see the data from ongoing pivotal trials comparing intravenous dose-dense chemotherapy with intraperitoneal chemotherapy, expected out within 5 years.

It may be that we have to see the comparison of all of these trials before we come up with what’s best for what group. It’s obviously critical to continue to emphasize the quality of life analyses of all these trials because just like the MITO-7 trial, it may come down to what the patients tolerate better – what do they feel is the better treatment for them.

Dr. Jonathan Berek is a professor and gynecologic oncologist at the Stanford (Calif.) University. Dr. Berek was the invited discussant of the study and disclosed no relevant conflicts of interest.


 

AT THE ASCO ANNUAL MEETING 2013

CHICAGO – Patients with advanced ovarian cancer may now have a less toxic but acceptably efficacious option when it comes to first-line chemotherapy, based on the final results of the Multicenter Italian Trials in Ovarian Cancer collaborative group’s trial 7 (MITO-7).

A total of 822 women were randomized to receive either the standard every-3-week regimen of chemotherapy – carboplatin with area under the curve (AUC 6) plus paclitaxel 175 mg/m² on day 1 every 21 days for six cycles – or to get a weekly regimen – carboplatin AUC 2 plus paclitaxel 60 mg/m² weekly for 18 administrations.

Trial results, reported at the annual meeting of the American Society of Clinical Oncology, showed that the weekly group did not have better progression-free or overall survival than did the group treated once every 3 weeks. But the weekly group did have lower rates of toxicities such as alopecia, neuropathy, and febrile neutropenia, as well as a better quality of life.

"Given the observed confidence intervals of progression-free survival, MITO-7 quality of life and toxicity data further support the use of a weekly schedule as first-line therapy for advanced ovarian cancer," commented lead investigator Dr. Sandro Pignata, a urogynecologist with Italy’s National Cancer Institute in Naples.

The patients studied by Dr. Pignata’s team had FIGO stage IC to IV ovarian, fallopian tube, or primary peritoneal cancer and had not previously received chemotherapy. Most were treated on the Italian MITO-7 trial, although some were treated on the Italian MANGO trial or the French ARCAGY GINECO trial.

The proportion receiving all planned cycles of chemotherapy was 85% in the weekly group and 91% in the 3-weekly group, he reported.

With a median follow-up of 19.9 months, the rate of progression-free survival was 18.8 months and 16.5 months, respectively, a nonsignificant difference. The findings were the same in subgroup analyses. There was also no significant difference in overall survival.

Quality of life measured with the FACT-O TOI (Functional Assessment of Cancer Therapy, for ovarian cancer, Trial Outcome Index) during the first 9 weeks of therapy (the trial’s other primary endpoint) was significantly better in the weekly treatment group.

With the weekly regimen, scores worsened slightly 1 week after the first administration but remained stable thereafter, according to Dr. Pignata. In contrast, with the 3-weekly regimen, scores worsened 1 week after each course of chemotherapy.

In terms of adverse events, the weekly group had significantly lower rates of grade 3 or worse neutropenia (39% vs. 50%), febrile neutropenia (less than 1% vs. 3%), thrombocytopenia (1% vs. 7%), and renal toxicity (0% vs. 2%); grade 2 alopecia (28% vs. 58%); and grade 2 or higher neuropathy (6% vs. 16%).

"The rate of severe allergic reaction or any-grade allergic reaction was not statistically significantly different," he pointed out. Also, "I want to underline that a significant proportion of patients treated with this weekly regimen...completed 18 weeks of therapy without losing their hair."

Dr. Pignata disclosed no relevant conflicts of interest.

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