Meta-Analysis Actually Shows Fewer Serious Adverse Events
Ameta-analysis reported at the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO) supports the new guidelines that recommend weight-based chemotherapy dosing for obese cancer patients.1,2
“We found that grade 3/4 toxicities—hematologic and overall—are actually less in obese patients versus normal-weight patients, which is not what people predict,” said Kathryn C. Hourdequin, MD, of the Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. “We should not be reducing chemotherapy doses in obese patients, which is what’s still happening in up to 40% of patients at this point.”
While chemotherapy dosing should be weight-based, it is not always done in clinical practice when the patient
is obese. The problem is that with weight-based dosing, obese patients can receive doses of chemotherapy that seem inappropriately large, she said.
“As a result, many oncologists fear there will be excess toxicity, and they respond by reducing the doses in obese patients,” she said. “Up to 40% of obese patients receive reduced doses, and evidence suggests that reducing chemotherapy doses or dose-intensities from the recommended standards may negatively impact survival.”
Hourdequin and her team conducted a systematic review of the literature and identified studies that compared outcomes of obese versus normal-weight adults receiving chemotherapy dosed according to actual body weight. The studies followed subjects for at least 1 cycle of chemotherapy and reported at least 1 prespecified outcome.
Of 3921 studies, 5 met the inclusion criteria, for a total of 6877 subjects treated between 1995 and 2012. The review included 21 chemotherapy agents and 13 different cancers, suggesting the results have broad applicability among many commonly used chemotherapy agents.
The majority of studies concluded that when chemotherapy was dosed by actual body weight, toxicity was lower or no different in obese versus normal-weight patients. This was true for any grade 3/4 toxicity, for grade 3/4 hematologic toxicity, and by leukocyte nadir, Hourdequin said.
In 3 studies, any grade 3/4 toxicity was observed in 556 of 1310 obese patients and in 1527 of 3847 normal-weight patients, which produced an odds ratio of 0.74 favoring obese patients (P <.0001). In 3 studies, there were 182 grade 3/4 hematologic adverse events among 1480 obese patients and 493 events among 2873 normal-weight patients, for an odds ratio of 0.73 favoring the obese patients (P = .04).
A study that compared leukocyte nadirs had variable results, depending on the regimen, dosing, and patient comorbidities. Three studies reported other toxicities (change in platelets, change in white blood cell counts, documented infections, and so forth), with variable findings.
Three of 4 studies reported reduced overall survival in obese patients, though none of the studies reported a statistically significant difference.
“It would be a jump to recommend higher doses, but at a minimum we should not be reducing dosing in these patients,” Hourdequin concluded.
- Hourdequin KC, Schpero WL, Piazik BL, et al. Toxicity of chemotherapy dosing using actual body weight in obese versus normal-weight patients: a systematic review and meta-analysis. Poster presented at: 2012 ASCO Annual Meeting; June 1-5, 2012; Chicago, IL.
- Griggs JJ, Mangu PB, Anderson H, et al. Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2012;30(13):1553-1561.