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Second-line docetaxel benefits seen for esophagogastric cancers

Publish date: January 23, 2013
By
Sherry Boschert

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A model study to guide supportive care

It’s extremely difficult to conduct studies comparing an active therapy like chemotherapy treatment vs. a supportive care approach, because patients and their physicians tend to have biases that make random assignment particularly difficult to accept. That said, there are important questions in oncology for which a supportive care arm is appropriate, both because treatments often have side effects, and there’s concern for worsening of quality of life, and there are situations where treatment is commonly given, but there may not be the level of evidence you’d like to see, like we have in front-line therapy.

This very important study shows two things: One, that second-line therapy in patients with esophagus and gastric cancers is of benefit in prolonging survival. In addition, there’s a quality of life benefit – so there’s not detriment to patients from the side effects of this treatment.


Dr. Neal J. Meropol

It’s really important to note that supportive care isn’t no-therapy. Supportive care means that there is an agreement that the goals of therapy are different than the goals of curative chemotherapy. But it’s still treatment, it’s still aggressive treatment, and it has specific goals.

There’s a lot of concern amongst the oncology community and beyond about how we approach the care of patients at the extremes, at the very end of life. There is significant evidence that a lot of treatment is given to patients within weeks of their death. Because treatment is toxic, we’re very cognizant of the question of whether patients are being harmed by this type of aggressive therapy.

This study is a critical type of study for providing an evidence base to help guide our treatment decisions at points in times when the goals are palliative and not curative, and where we’re talking about modest prolongations in survival. This is really a model for a type of study that we’d like to see more of, both from a clinical outcomes point of view and, of course, when evaluating health care costs.

Oncology, as a field, is one of the most clearly evidence-based fields of medicine. Most of what we do is based on high levels of evidence. Treatment towards the end of life is an area where perhaps we’ve fallen a little short and need to pay additional attention.

Dr. Neal J. Meropol is chief of hematology and oncology at Case Western Reserve University, Cleveland. He gave these comments as moderator of the press briefing. He has been a consultant or adviser to Precision Therapeutics.


 

FROM A PRESS BRIEFING SPONSORED BY THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY

Results of a phase III trial support a common clinical practice – giving docetaxel as second-line chemotherapy to patients with advanced adenocarcinomas of the stomach or esophagus that progressed after first-line chemotherapy.

The randomized, controlled, open-label study showed significantly longer overall survival in 84 patients who received docetaxel (a median of 5.2 months), compared with 84 patients who received only "active symptom control" as second-line therapy (3.6 months), Dr. Hugo Ford reported. Active symptom control could include anything that the treating clinicians felt might be appropriate to manage symptoms, including radiotherapy, steroids, and supportive medications.

Dr. Hugo Ford

The finding bolsters previous, weaker evidence of survival benefit from second-line chemotherapy in these patients. Perhaps more important, though, is the current study’s finding of improved quality of life in patients who underwent second-line chemotherapy with docetaxel, compared with no second-line chemotherapy, he said.

Although scores for global quality of life and function did not differ significantly between groups, pain scores were significantly better in the treatment group than the control group, Dr. Ford said during a press briefing sponsored by the American Society for Clinical Oncology (ASCO).

"This is the first trial to show a quality of life benefit" from second-line chemotherapy in patients with esophagogastric cancer, "which is a very important finding in terms of informing patients about the likely benefits of the treatment we’re offering them," added Dr. Ford, director of cancer services at Addenbrooke’s Hospital, Cambridge, England. "Docetaxel should be a standard second-line treatment for esophagogastric adenocarcinoma."

He will present the findings in San Francisco on Jan. 24 at a meeting on gastrointestinal cancers sponsored by ASCO.

Clinicians in the United States and Europe commonly give second-line chemotherapy to patients with advanced esophagogastric cancers that progress after first-line treatment, despite a lack of strong evidence for the practice. Without second-line chemotherapy, the median survival time of patients who relapse after first-line chemotherapy for advanced esophagogastric adenocarcinoma is 3-4 months, previous data suggest.

Two separate trials recently reported small survival benefits from second-line chemotherapy using other drugs. A German study using irinotecan was too small (only 40 patients) to be considered robust evidence, Dr. Ford said. A Korean study used either irinotecan or docetaxel for second-line therapy but included only gastric cancers in patients who were Asian and younger and fitter than patients normally seen in U.S. practices, he added.

Paclitaxel also is used commonly as second-line chemotherapy for esophagogastric cancers and similar to docetaxel. Although there are no randomized data showing benefits from second-line paclitaxel, compared with supportive care, "one would be reasonable extrapolating a benefit there," he said.

The current trial enrolled patients with locally advanced or metastatic esophagogastric cancer who had a performance status of 0-2 and whose cancer had progressed within 6 months of first-line chemotherapy with platinum/fluoropyrimidine. Patients randomized to second-line docetaxel received IV 75 mg/m2 every 3 weeks for up to six cycles.

Only 19 patients in the docetaxel group completed six cycles of the chemotherapy (23%); the median number of cycles was three per patient. Disease progression and toxicity were the main reasons for not completing six cycles. Grade 4 toxicity occurred in 18 patients on docetaxel (21%).

Nearly a third of patients in the docetaxel group received either one round or no chemotherapy, which points to the generally poor prognosis with this aggressive disease and the fact that a significant number of patients will not benefit from chemotherapy, Dr. Ford said.

"For me, it makes the case that in those people that are benefitting from chemotherapy, the benefits are probably more marked even than we saw in the trial," he said.

The study was unable to identify any subgroup as being less likely to benefit from second-line chemotherapy. Future studies may try to find ways to identify patients who won’t benefit from the treatment, he said.

"Docetaxel should be standard second-line treatment for esophagogastric adenocarcinoma, and we think it’s likely to be the standard arm against which future treatments should be compared," Dr. Ford said.

After second-line chemotherapy, 7% of patients had a partial response, and 46% had stable disease.

The median age in the study was 65 years, and 81% of patients were male. The performance status at randomization was 0 in 27% of patients, 1 in 57%, and 2 in 15%. A total of 46% of cancers were in the stomach, 34% were in the esophagogastric junction, and 20% were in the esophagus. The disease had metastasized in 86% of patients.

Disease progression occurred during primary chemotherapy in 43% of patients, within 3 months of finishing primary chemotherapy in 28%, and between 3 and 6 months after primary chemotherapy in 29% of patients.

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