SEVERE LYMPHOCYTOPENIA AND INTERSTITIAL PNEUMONIA IN PATIENTS TREATEDWITH PACLITAXEL AND SIMULTANEOUS RADIOTHERAPY FOR NON-SMALL-CELL LUNG-CANCER

Purpose: In a phase II trial with paclitaxel and simultaneous radiothe rapy in non-small-cell lung cancer (NSCLC) patients, an unexpected hig h incidence of interstitial pneumonias was observed. The type of immun odeficiency associated with this treatment approach is characterised. Patients and Methods: Fifteen patients with inoperable stage IIIA/B NS CLC were treated with paclitaxel as a 3-hour infusion on day 1 in week s 1 to 3 and 6 to 8 at dose levels between 50 mg/m(2) and 86 mg/m(2) a nd with simultaneous radiotherapy in daily doses of 2 Gy, 5 days per w eek, in weeks 1 to 3 and 6 to 8 up to a total dose of 56 Gy. Hematolog ic parameters and lymphocyte subsets were monitored. Results: Fourteen patients are assessable for response. The overall response rate was 7 8%, with four major responses, six partial remissions, and four minor responses. The major toxic effect observed was a moderate to severe pr otracted lymphocytopenia (380 +/- 310/mu L) in all patients. Seven pat ients developed moderate to severe interstitial pneumonia; one had an additional herpes tester infection, while an eighth patient had a cyto megalovirus infection. During treatment, all lymphocyte subsets were r educed, 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 pro motes opportunistic infections. Long-term antibiotic and antimycotic p rophylaxis 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 Am erican Society of Clinical Oncology.