CONTINUE CHEMOTHERAPY FOR METASTATIC BREAST CANCER FOR AS LONG AS POSSIBLE?

October 10, 2010 (Milan, Italy) — Prolonging first-line chemotherapy in metastatic breast cancer delays disease progression and rate of death, according to the results of a meta-analysis presented here at the 35th European Society for Medical Oncology Congress.

"Our review suggests that longer duration of first-line chemotherapy, until disease progression or for a predetermined number of cycles, shows a 36% decrease in the rate of disease progression," said lead author Alessandra Gennari, MD, a medical oncologist from Galliera Hospital in Genova, Italy.

"This was clinically meaningful and statistically significant, and there was a 9% decrease in the rate of death," she told Medscape Medical News.

The optimum duration of first-line chemotherapy is still poorly defined. Dr .Gennari explained that in the United States, chemotherapy is usually administered until disease progression, but in Europe, practice is unclear. "Many European oncologists stop chemotherapy after a predetermined number of cycles, with duration of chemotherapy dictated by patient tolerability, responsiveness, and physician preferences."

"The first thing patients ask when they receive chemotherapy is, 'How long must this treatment continue?' and the best response we can give is, 'As long as you can cope with it,' " Dr. Gennari emphasized. "We know that if we stop chemotherapy then the disease will progress, but if we prolong therapy then, of course, disease will progress sooner or later, but we know it will actually be later,"

The US National Comprehensive Cancer Network guidelines state that: "Due to the lack of overall survival differences, the use of prolonged versus shorter chemotherapy needs to be weighted against the detrimental effects of continuous chemotherapy on overall quality of life." Dr. Gennari pointed out that their results justify a physician proposing to a patient that they prolong chemotherapy treatment because the patient may gain in survival.

Prolonging Therapy Delays Progression

By conducting a meta-analysis of 11 trials dating back 30 years, Dr. Gennari and colleagues set out to determine the effect of extending chemotherapy beyond a predetermined number of cycles on progression-free survival and overall survival in patients with metastatic breast cancer. A total of 2269 cases were reviewed.

Results showed a statistically significant and clinically meaningful advantage in time to disease progression. There was a 36% (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.55 - 0.76) decrease in the hazard of disease progression, which was statistically significant, but also a 9% (HR, 0.91; 95% CI, 0.84 - 0.99) decrease in the hazard of death.

"This confirms what we see in terms of progression-free survival, but importantly, it justifies what we tell our patients — which is that they must continue chemotherapy after disease control had been achieved," Dr. Gennari said.

The magnitude of the effect of longer chemotherapy precipitating a decrease in rate of progression and death was similar across all trials, suggesting independence from different factors such as time of randomization (P = .91), study design (P = .2), number of cycles in the control group (P = .6), and endocrine therapy (P = .6). "This shows that the magnitude of the effect that we see is independent of other factors and is possibly truly a reflection of chemotherapy duration," she explained.

Questions Remain

In conclusion, Dr. Gennari acknowledged that a number of open questions remain and require addressing with new clinical trials. For example, what is the optimal prolonged regimen? Should the same chemotherapy be administered until toxicity or disease progression? Should predetermined sequences be planned with single agents, or is there a role for prolonged low-dose chemotherapy avoiding the toxic doses? And what is the optimal association of chemotherapy with targeted agents such as anti-angiogenesis, anti-HER2?

Offering an independent comment, John Pippen, MD, a medical oncologist from Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, said that "I feel we should really follow patients in terms of toxicity and quality of life, and as long as that is not compromised, then it is reasonable to continue."

"In certain situations, such as the palliative situation of my study, tolerability was very good, and we want patients to stay on therapy as long as they tolerate it," he added.

Also adding further comment, Francesco de Lorenzo, MD, president of the Italian Association of Cancer Patients; professor of biochemistry at the University of Naples, Italy; and a cancer survivor who received chemotherapy, said that therapy decisions should be made on evidence-based information.

"Sometimes patients ask for more treatment, but the clinician has to make an independent decision," he said in an interview. "We need more research and evidence of the effect of chemotherapy in prevention. But also, we need to consider that when chemotherapy is toxic, then quality of life and cost/benefits should be seriously considered.

"I don't know if available evidence justifies more chemotherapy. Sometimes patients ask me, 'Why should I live just for more chemotherapy?' Patients need to be informed of costs and benefits of continuing cycles," he told Medscape Medical News.

Dr. Gennari, Dr. Pippen, and Dr. de Lorenzo have disclosed no relevant financial relationships.

35th European Society for Medical Oncology Congress: Abstract 276O. Presented October 10, 2010.