Paclitaxel/carboplatin prior to surgery is safe and feasible in early stage non-small cell lung cancer. The treatment did not compromise surgical morbidity or mortality rates. The relapse patterns were similar to historical series. The survival rates are encouraging.

Survival is poor in patients with early stage non-small cell lung cancer. The typical 5-year survival rates range from a low of 9% to a high of 38%, according to Dr. Pisters. Studies of postoperative (adjuvant) chemotherapy have not demonstrated a survival benefit in this population. However, induction chemotherapy has shown a survival benefit in some trials of patients with later stage non-small cell lung cancer.

Accordingly, Dr. Pisters and colleagues undertook a study evaluating the feasibility of administering chemotherapy prior to resection in patients with early stage lung cancer. Results of this phase II trial were published in 2000 showing the feasibility of paclitaxel/carboplatin chemotherapy prior to surgery. Here at ASCO, Dr. Pisters reported longer-term follow-up data. The mean follow-up was 4.8 years from time of study entry.

All patients had clinical stage T2N0, T1-2N1 or T3N0-1 disease. A total of 133 eligible patients accrued into the study. They had very typical baseline characteristics for non-small cell lung cancer.

Patients received paclitaxel (225 mg/m² over 3 hours) and carboplatin every 21 days before and after surgery. One cohort of patients received 2 cycles before surgery and 3 cycles after surgery. A second cohort received 3 cycles before surgery and 2 cycles afterward. Most of the patients did receive all of the planned preoperative chemotherapy. However, less than half could receive the postoperative chemotherapy cycles.

Dr. Pisters said the response rate to the chemotherapy was encouraging: 56% in the first cohort and 44% in the second cohort.

The toxicities were very typical and included mainly granulocytopenia (36% and 51% in the first and second cohorts, respectively).

Overall, 95% of patients in the trial did undergo surgical exploration, and 86% had complete removal of tumor. There was a 5% incidence of pathologic complete response (investigators found no viable tumor in the resected specimen).

Investigators have documented recurrence in 61 (about 46%) of patients. Most of these recurrences (44%) were distant. The rest were in brain only (21%), local and distant (18%) and local only (15%). This relapse data is similar to data from surgical only control series.

For the entire cohort of subjects, the 1-year, 3-year and 5-year survival rates were 84%, 58% and 45%, respectively. It is difficult to compare those survival rates to historical experience. However, Dr. Pisters said the anticipated 5-year survival rate of T2N0 patients treated with surgery is 38%. Because many patients in this preoperative chemotherapy trial had more advanced disease, that 45% 5-year survival rate was encouraging to investigators.

These results suggest the use of paclitaxel/carboplatin before surgery is safe, feasible and does not compromise surgical morbidity and mortality rates. The relapse patterns are similar to historical series and the survival rates are encouraging.

Investigators are currently conducting a high-priority Intergroup trial (SWOG 9900). This trial includes participation from most of the cooperative groups in the United States and Canada. Investigators plan to enroll 600 patients with early non-small lung cancer. Randomization is to preoperative chemotherapy with 3 cycles of paclitaxel/carboplatin followed by surgery versus immediate surgery.

Dr. Pisters said she is hopeful the preoperative chemotherapy approach will improve survival versus surgery alone, as it has in other tumor types. Eventually, investigators may incorporate better or targeted agents into a preoperative chemotherapy regimen. For now, however, the results of this trial may new hope to patients with early stage non-small cell lung cancer.