New Guidelines Favor Chemo as Adjuvant Therapy for NSCLC
Developed by expert panels convened by the American Society of Clinical Oncology (ASCO) and Cancer Care Ontario, the guidelines recommend the use of adjuvant chemotherapy in patients with stages IIA, IIB, or IIIA NSCLC in which the tumors have been completely resected. In most of these cases, disease has spread to nearby lymph nodes.
Until the current decade, explains guidelines panel co-chair Dr. Katherine M.W. Pisters of M.D. Anderson Cancer Center, randomized clinical trials of adjuvant therapy for NSCLC had reported negative or inconclusive results.
"It's really only been in the last 5 to 6 years that we've had positive data," she says. "These more modern trials have had better designs with larger numbers of patients studied and more homogeneous patient populations enrolled. And the chemotherapy regimens used in these trials are more effective against NSCLC than the regimens employed in older trials."
Oncologists are urged in the guidelines to embrace adjuvant chemotherapy for the appropriate patients with NSCLC.
"The guideline panel concludes that the therapeutic nihilism toward adjuvant chemotherapy for stage II-III NSCLC should now be abandoned," the panel wrote. "The findings and recommendations contained in this guideline provide clinicians with the evidentiary basis for a firm commitment to treat these patients."
Part of oncologists' reluctance to use adjuvant chemotherapy, explains Dr. Giuseppe Giaccone, chief of the Medical Oncology Branch in NCI's Center for Cancer Research, is based on patients' poor tolerance of chemotherapy after having undergone a thoracotomy - opening up the chest wall to access the lungs and remove the tumors.
"That is a major issue," Dr. Giaccone says. "In only about 70 percent or less of patients can full-dose chemo be delivered after that operation." But now, with several trials having demonstrated a clear survival benefit of adjuvant chemotherapy, he continues, that reticence "has to change."
In two cases, the guidelines note some positive, but inconclusive, data on adjuvant treatment options: adjuvant chemotherapy for stage IB patients and adjuvant radiotherapy for stage IIIA patients.
For patients with stage IB disease (a localized, larger tumor with a strong likelihood of spreading to nearby lymph nodes), says Dr. Pisters, "the trends are there," but the data are not strong enough at the moment to recommend routine use of adjuvant chemotherapy. At the 2006 ASCO annual meeting, longer-term data presented from a randomized clinical trial of only stage IB patients, the CALGB 9633 trial, showed no statistically significant overall survival benefit, although the data still trended in favor of adjuvant chemotherapy. An unplanned subset analysis, however, revealed a statistically significant benefit in patients with tumors 4 cm or larger.
"It's very complicated," Dr. Pisters admits. Oncologists "have got to sit down and talk to their [IB] patients about whether adjuvant therapy is right for them."
As for adjuvant radiotherapy, two studies have suggested it may be beneficial in stage IIIA patients. But without data from prospective, randomized clinical trials that directly addressed this issue, the panel believed the current evidence was insufficient to recommend adjuvant radiation in all stage IIIA patients.
Oncologists generally eschew adjuvant radiotherapy in their NSCLC patients, Dr. Giaccone notes, but stage IIIA is an exception. "The chance of local relapse is high in these patients," he says. "So having something that could prevent local relapse is an attractive option."
Also included in the guidelines are recommendations - which the panel acknowledged were not necessarily "evidence-based" - for communicating with patients about adjuvant therapy.
Among the recommendations is dedicating a single office session to a discussion about adjuvant therapy. The discussion, the panel suggested, should cover factors beyond survival, such as the side effects of adjuvant therapy and its potential effect on quality of life. The guidelines also provide a sample chart that allows patients to more clearly see the absolute survival benefit adjuvant therapy conferred in recent clinical trials.