Ovarian Cancer Survival Reduced with Chemotherapy Dose Reduction

Paclitaxel and carboplatin dose reductions are unnecessary for obese ovarian cancer patients

medwireNews: Ovarian cancer chemotherapy regimens should not be tailored to the patient’s body size, say researchers who found that survival is adversely affected by reduced doses of paclitaxel and carboplatin.

“Oncologists are often reticent to use full doses in obese women because of concern for toxicity and thus cap the dose”, explain ELISA Bandera, from Rutgers Cancer Institute of New Jersey in New Brunswick, USA, and co-authors in JAMA Oncology.

“Our study showed that neither survival nor toxicity is worse in obese women given full drug doses of chemotherapy.”

The review of 806 patients receiving first-line chemotherapy with curative intent indicated that a high body mass index (BMI) was the most common reason cited for dose reduction.

The odds ratio (OR) for dose reduction, defined as a relative dose intensity (RDI) of less than 85%, was 2.85 for obese women with a BMI of 30.00 to 34.99 kg/m2 versus women with a normal BMI of 18.50 to 24.99 kg/m2, rising to an OR of 19.85 for those with a BMI of 40 kg/m2 or higher.

BMI and actual total dose of paclitaxel and carboplatin negatively correlated, so that women with an obese BMI of 40 kg/m2 or above were given doses 38% and 45% lower, respectively, than women with a normal BMI.

Obesity at time of ovarian cancer diagnosis was a positive predictor of overall survival after adjusting for factors such as age, tumour characteristics and comorbidity, with HRs for mortality of between 0.55 to 0.86 versus a normal BMI. The corresponding HRs for ovarian cancer-specific survival ranged between 0.53 and 0.88.

Both overall survival and ovarian cancer-specific survival were also significantly lower in patients with an average RDI of less than 70% compared with an average RDI of 85% to 100%, with HRs for mortality of 1.62 and 1.69, respectively.

When the impact of BMI and RDI were assessed together, women with a normal BMI who received an average RDI of 85% or less had poorer survival than those with a higher average RDI (HR=1.50).

Moreover, the possible survival benefit associated with obesity “disappeared” after taking into account dose reduction and was no longer significant, the researchers say.

Side effects were more likely in patients receiving a lower RDI, which the researchers believe “is likely a reflection of chemotoxic effects resulting in decisions to reduce dose.”

But obese patients were less likely than their normal BMI peers to experience neutropenia, and BMI did not predict neuropathy.

In an accompanying comment, S Percy Ivy, from the National Cancer Institute in Bethesda, Maryland, USA, and Jan Beumer, from the University of Pittsburgh in Pennsylvania, USA, call dosing decisions based on size “both an art and a science until definitive data are generated”.

Recommending the development of a database to avoid the need for very large randomised studies to tease out the impact of BMI, RDI, body surface area and other factors on dose, they conclude: “Clinical investigators need to apply the approaches and lessons learned with paclitaxel and carboplatin to other drugs used for the treatment of ovarian cancer: cisplatin, gemcitabine, liposomal doxorubicin, bevacizumab, olaparib, cediranib, and others.

“Loss of RDI at higher BMI will certainly be a problem for some [of] these drugs”.

References

Bandera EV, Lee VS, Rodriguez-Rodriguez L, et al. Impact of chemotherapy dosing on ovarian cancer survival according to body mass index. JAMA Oncol; Advance online publication 2 July 2015. doi:10.1001/jamaoncol.2015.1796

Ivy SP, Beumer JH. Ovarian cancer survival and chemotherapy dosing, body mass index, and body surface area. Are we there yet? JAMA Oncol; Advance online publication 2 July 2015. doi:10.1001/jamaoncol.2015.1926

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