Evidence
Alert

First-line chemotherapy for ovarian cancer given once every three weeks may preserve quality of life

Women with a new diagnosis of ovarian cancer receiving weekly chemotherapy may have reduced quality of life compared to those receiving treatment every three weeks because the more frequent treatment may cause long-lasting nerve damage.

Ovarian cancer is usually treated every three weeks with chemotherapy containing the medicines carboplatin and paclitaxel. A study in Japan challenged this standard of care. It found that giving chemotherapy more frequently – weekly instead of every three weeks – improved survival without reducing quality of life.

However, the largest study to date on newly-diagnosed ovarian cancer, called ICON8, reported no survival advantage with weekly treatment.

The study reported here looked at the quality of life of patients in ICON8. Researchers found that patients who received weekly paclitaxel had poorer quality of life during treatment. They were also more likely to have nerve damage that lasted up to 18 months.

Researchers concluded that the standard care for ovarian cancer should not change. Chemotherapy should not be given more frequently than every three weeks.

What’s the issue?

Standard therapy for ovarian cancer is surgery to remove the tumour plus chemotherapy. Two medicines, carboplatin and paclitaxel, are given once every three weeks for six sessions.

A smaller study in Japan found that giving paclitaxel every week, and carboplatin every three weeks, improved survival. Women with ovarian cancer lived three years longer than those receiving standard three-weekly treatment. Their quality of life was not harmed by the weekly treatment in this study.

However, ICON8, conducted among women mostly of European descent, did not support the Japanese findings. Unlike in the Japanese study, European patients in ICON8 had similar survival regardless of whether paclitaxel was given weekly or every three weeks. This suggests that Asian and White women may respond differently to the increased dose of paclitaxel.

The current study looked at whether weekly treatment affected the general well-being of women in ICON8.

What’s new?

1438 women with ovarian cancer were asked about their quality of life at regular intervals for up to five years after starting treatment. They completed written questionnaires on factors such as emotional well-being, fatigue and nerve pain.

Nine months after patients entered the trial, the researchers found:

  • Patient well-being fell during chemotherapy but then improved over the following months regardless of which treatment was given
  • When researchers looked at well-being scores during and after treatment, those on weekly treatment experienced lower quality of life compared to those receiving treatment every three weeks
  • Nerve damage caused by paclitaxel was worse in the weekly treatment arms and persisted for longer. It started later than in women receiving chemotherapy every three weeks
  • Patients having weekly treatment reported slightly increased levels of fatigue compared to those treated every three weeks but this was not significant.

Why is this important?

Measuring patient well-being for different treatments helps doctors make more informed choices about the best way to help a patient.

Although survival was similar for patients on all treatment plans, well-being data shows a different story. The study suggested weekly schedules were harder for patients to tolerate and caused long-lasting toxicity compared to less frequent chemotherapy.

The researchers believe that three-weekly chemotherapy should remain the standard of care for most newly-diagnosed ovarian cancer patients.

Most women with ovarian cancer have surgery to remove as much of the cancer as possible, followed by chemotherapy. The researchers believe these women will not benefit from chemotherapy given more frequently than every three weeks.

However, some women start treatment with chemotherapy and have their surgery delayed. These women are likely to be in poorer health than women who have surgery upfront and the researchers say this smaller group might still benefit from weekly chemotherapy.

What’s next?

It is not known why paclitaxel causes nerve damage. The study found the numbness to hands and feet that occurs following weekly paclitaxel treatment is slower to develop but lasts longer than following three weekly treatment. The researchers believe long-lasting nerve damage and numbness are likely because the total amount of paclitaxel given is higher for people taking weekly treatment. More research is needed on this aspect.

There may be better ways to assess patient well-being than paper questionnaires. In future studies, this could be done online or via wearable technology.

You may be interested to read

The full paper: Blagden SP, and others.Weekly platinum-based chemotherapy versus 3-weekly platinum-based chemotherapy for newly diagnosed ovarian cancer (ICON8): quality-of-life results of a phase 3, randomised, controlled trial. The Lancet Oncology. 2020;21:969-977

The original ICON8 trial report: Clamp AR, and others. Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal carcinoma treatment (ICON8): primary progression free survival analysis results from a GCIG phase 3 randomised controlled trial. The Lancet. 2019;394:2084-2095

The Japan study of weekly vs three-weekly chemotherapy in ovarian cancer: Katsumata N, and others. Japanese Gynecologic Oncology Group. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. The Lancet. 2009;378:1331-1338

Funding

The research was funded by Cancer Research UK, Medical Research Council, Health Research Board Ireland, Irish Cancer Society, and Cancer Australia. It was supported by NIHR Biomedical Research Centre.

Commentaries

Study author

The key take-home message is to include quality of life assessment into studies. But assessing patient wellbeing is meaningless unless it asks the right questions and is assessed frequently.

I was surprised that the ICON8 study outcome was so different to the study in Japan. Why did the Japanese patients respond so much better to weekly paclitaxel-containing treatment? We still don’t have an answer to this question. We need to know if Asian ovarian cancer patients living in the UK would be better off receiving weekly paclitaxel rather than the standard 3-weekly treatment.

Sarah Blagden, Associate Professor of Experimental Cancer Therapeutics, University of Oxford

Cancer Patient

I am reassured that efforts are being made to reduce the side effects of cancer patients and to consider patients’ quality of life.

Given the choice, and as a patient I should be given the choice, I would always opt for a shorter, meaningful life rather than a longer, less meaningful one, for being able to live rather than merely exist, able to do things, connect, stay involved, be a participant in life rather than an observer of other people’s lives. Doctors and researchers need to approach situations from a “whole person”  viewpoint,  and decisions affecting the lives and wellbeing of patients and their families need to be shared by doctors and patients, made with them, not for them. Patients need to be involved at every stage of decision-making, clinicians empathising with patients and asking themselves the questions they would want answers to if they, and their families, were facing the same situation.

Ann, Nottingham

Conflicts of Interest

None declared