Severe lymphocytopenia and interstitial pneumonia in patients treated with paclitaxel and simultaneous radiotherapy for non-small-cell lung cancer

Purpose: In a phase II trial with paclitaxel and simultaneous radiotherapy in non-small-cell lung cancer (NSCLC) patients, an unexpected high incidence of interstitial pneumonias was observed. The type of immunodeficiency associated with this treatment approach is characterised. Patients and Methods: Fifteen patients with inoperable stage IIIA/B NSCLC were treated with paclitaxel as a 3-hour infusion on day 1 in weeks 1 to 3 and 6 to 8 at dose levels between 50 mg/m(2) and 86 mg/m(2) and with simultaneous radiotherapy in daily doses of 2 Gy, 5 days per week, in weeks 1 to 3 and 6 to 8 up to a total dose of 56 Gy. Hematologic parameters and lymphocyte subsets were monitored. Results: Fourteen patients are assessable for response. The overall response rate was 78%, with four major responses, six partial remissions, and four minor responses. The major toxic effect observed was a moderate to severe protracted lymphocytopenia (380 +/- 310/mu L) in all patients. Seven patients developed moderate to severe interstitial pneumonia; one had an additional herpes tester infection, while an eighth patient had a cytomegalovirus infection. During treatment, all lymphocyte subsets were reduced, as follows (n = 9, mean +/- SD): CD4(+) T cells (100 +/- 90/mu L), CD8(+) T cells (130 +/- 160/mu L), natural killer (NK) cells (70 +/- 80/mu L), and B cells (20 +/- 10/mu L). Thus, the most pronounced toxicity was seen in CD4(+) T cells and B cells. There was no recovery of lymphocyte subsets during a 3-month follow-up period. Conclusion: Paclitaxel with simultaneous radiation induces lymphocytopenia and promotes opportunistic infections. Long-term antibiotic and antimycotic prophylaxis is recommended. Whether the lymphocytopenia is an additive effect of paclitaxel and radiation or whether it can be induced by low-dose weekly paclitaxel alone remains to be determined. (C) 1996 by American Society of Clinical Oncology.