IASLC: Aggressive Induction Therapy Feasible for Some NSCLC Patients

SEOUL, South Korea, Sept. 4 -- Aggressive induction therapy for locally advanced but operable non-small-cell lung cancer (NSCLC) appears safe and feasible, with hints of survival and surgical advantages.

The addition of chemotherapy to radiotherapy before surgery did not increase perioperative morbidity or affect postoperative care, researchers reported in a small German study presented here at the International Association for the Study of Lung Cancer meeting.

Underpowered, the study found nonsignificant trends suggesting that trimodal therapy nearly doubled median survival (29 months versus 15, P=0.15) and halved the number of patients needing extensive surgery (11 versus 22, P=0.10) compared with radiation and surgery alone, reported Wilfried E. Eberhardt, M.D., of the University of Duisburg-Essen in Essen, Germany, and colleagues.

The findings help lay to rest the arguments against trimodal therapy that arose after a North American Intergroup trial comparing chemoradiation followed by surgery to chemoradiation alone, Dr. Eberhardt said.

"People said the morbidity and mortality would be too high," he said.

So the researchers conducted a study of patients with stage IIIA non-small-cell lung cancer deemed operable by nodal status at mediastinoscopy (one or two lymph nodes involved, but no "bulky" N2 disease), a subset that represents less than 20% of stage IIIA cancers.

Because of slow accrual, the study was closed early with 106 patients.

Participants were randomized to surgery and 50 to 60 Gy radiotherapy or to three cycles of induction chemotherapy (cisplatin [Platinol] and etoposide), then concurrent radiochemotherapy (45 Gy, cisplatin and etoposide), prophylactic cranial irradiation, and, finally, surgery.

The researchers found similar perioperative morbidities and postoperative care outcomes in both groups. The difference between study arms was not significant for any outcomes, including:

• Stump insufficiency (P=0.86)
• Parenchym fistula (P=0.42)
• Heart rhythm disorders (P=0.90)
• Postoperative bleeding (P=0.10, higher in the trimodal arm)
• Postoperative infections (P=0.12, lower in the trimodal arm)
• Thromboembolic complications (P=0.89)
• Postoperative hospitalization (P=0.87)
• Time in intensive care unit (P=0.18)
• Time on postoperative respirator (P=0.25)

Major toxicities resulting in treatment-related death were one case of postoperative infection in the surgery and radiation arm versus one case of chemotherapy-induced infection, one case of tumor bleeding during chemotherapy, and one case of postoperative bleeding in the trimodal therapy group.

However, there were nonsignificant trends for organ-sparing surgery and improved survival in the trimodal therapy group.

Patients who received induction chemotherapy tended to have less extensive lobectomy or bilobectomy surgery rather than pneumonectomy (P=0.10). The surgical findings were:

• Only 11 of 40 patients (27.5%) in the trimodal therapy group who received surgery underwent pneumonectomy compared with 22 of 51 patients (43.1%) operated on in the radiation and surgery arm.
• Trimodal therapy patients were more likely to have simple pneumonectomy than extended pneumonectomy (seven versus four) whereas the opposite was true for the radiation and surgery arm (eight versus 14).
• The complete resection rate was 60% after intensive induction therapy.

Furthermore, median overall survival was nearly doubled with trimodal therapy, although not significantly so (29 months versus 15, P=0.15).

Likewise, median progression-free survival (15 months versus nine, P=0.20) and disease-specific survival (18 months versus 10, P=0.02) favored trimodal therapy.

"Because of the small number of patients randomized, survival results are inconclusive," Dr. Eberhardt cautioned, "although survival data favored trimodality in the first four years."

"Aggressive trimodality treatment remains a possible and valid strategy in this subset of locally advanced non-small-cell lung cancer patients," he concluded. "Selected patients may benefit from intensive induction protocols."