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


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/m2 and 86 mg/m2 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/microL) in all patients. Seven patients developed moderate to severe interstitial pneumonia; one had an additional herpes zoster 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/microL), CD8+ T cells (130 +/- 160/microL), natural killer (NK) cells (70 +/- 80/microL), and B cells (20 +/- 10/microL). Thus, the most pronounced toxicity was seen in CD4+ T and B cells. There was no recovery of lymphocyte subsets during a 3-month follow-up period.


CONCLUSIONS
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.
Reckzeh
B
B
Department of Internal Medicine, Division of Hematology/Oncology, Phillips-Universität, Marburg, Germany.
Merte
H
H
Pflüger
K H
KH
Pfab
R
R
Wolf
M
M
Havemann
K
K
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D004334:Drug Administration Schedule; D005434:Flow Cytometry; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000139:chemically induced / Q000209:etiology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D018655:Lymphocyte Count / Q000187:drug effects / Q000528:radiation effects; D008231:Lymphopenia / Q000139:chemically induced / Q000209:etiology*; D008875:Middle Aged; D009894:Opportunistic Infections / Q000209:etiology*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects*; D018714:Radiotherapy, Adjuvant
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel