Docetaxel (Taxotere) in the neo-adjuvant setting in non-small-cell lung cancer.

BACKGROUND

There is a potential for neo-adjuvant chemotherapy to provide significant benefit in outcome for patients with locally advanced non-small-cell lung cancer (NSCLC). Patients with N2/T3 NSCLC have a poor prognosis when treated by surgery alone since micrometastases result in relapse in the majority of cases. The same is true of patients with N3/T4 disease treated only with radiotherapy. Systemic therapy is therefore required, and cisplatin-based induction chemotherapy prior to surgery or radiotherapy has been shown to improve survival when compared with surgery or radiotherapy alone. Docetaxel has been shown to have significant activity in stage IV NSCLC and ongoing phase III trials are comparing single agent docetaxel or doceatxel in combination with cisplatin or VP16 before local treatment to local treatment alone.

DESIGN

Patients with locally-advanced (stage IIIa or IIIb) NSCLC receive three cycles of docetaxel (100 mg/m2) followed by appropriate local therapy, or local therapy alone. Local therapy for stage IIIa patients is surgery (with or without radiotherapy depending on completeness of resection) and for stage IIIb patients curative intent radiotherapy. In another on-going study in stage IIIa NSCLC, docetaxel (75 mg/m2) is given in combination with cisplatin (40 mg/m2) followed by surgery. Patients must have histologically or cytologically confirmed NSCLC, have received no prior treatment for the disease and are suitable to undergo surgery or radical radiotherapy, as appropriate.

RESULTS

Initial results from the phase III comparative study show that single agent docetaxel in the neo-adjuvant setting is effective and associated with acceptable toxicity. Two hundred of the planned two hundred ninety-two patients have been accrued to the single-agent docetaxel neo-adjuvant study. In the first 49 evaluable patients in the docetaxel arm, 1 CR and 18 PR have been achieved (response rate 39%) and no patients receiving docetaxel neo-adjuvant therapy have progressed. All patients were able to receive the full doses of docetaxel.

CONCLUSION

The details of time-to-progression and survival in this study will eventually confirm the results from recent small trials of neo-adjuvant chemotherapy in locally-advanced NSCLC.