Selective CD4+ lymphopenia in melanoma patients treated with temozolomide: A toxicity with therapeutic implications Journal Article
| Authors: | Su, Y. B.; Sohn, S.; Krown, S. E.; Livingston, P. O.; Wolchok, J. D.; Quinn, C.; Williams, L.; Foster, T.; Sepkowitz, K. A.; Chapman, P. B. |
| Article Title: | Selective CD4+ lymphopenia in melanoma patients treated with temozolomide: A toxicity with therapeutic implications |
| Abstract: | Purpose: Standard schedule temozolomide (TMZ; daily for 5 days every 4 weeks) is often used in melanoma patients, but phase III data show that it is no more effective than standard dacarbazine. Extended TMZ dosing regimens may be superior by delivering the drug continuously at a higher dose over time. Using an extended dosing schedule, we noted a high incidence of lymphopenia and occasional opportunistic infections (OIs). Here we report our retrospective experience in the first 97 patients. Materials and Methods: TMZ was administered at 75 mg/m2/d orally for 6 weeks every 8 weeks, although nine patients were treated continuously without a break. Seventeen patients were treated with TMZ alone; 73 patients received TMZ with thalidomide; seven patients received TMZ with low-dose interferon alfa. Results: Median duration of TMZ treatment was 113 days; 29% received ≥ 24 weeks of therapy. Lymphopenia was seen in 60% of patients (absolute lymphocyte count < 800/μL) with a median of 101 days to lymphopenia. TMZ did not cause significant neutropenia or thrombocytopenia. Lymphopenia was not more common in patients treated concomitantly with thalidomide. In all patients analyzed for lymphocyte subsets, lymphopenia induced by TMZ affected the CD4+ compartment preferentially. There were two documented OIs (Pneumocystis and Aspergillus pneumonia) as well as other infections indicative of T-cell dysfunction in another 21 patients. Conclusion: TMZ at this dose and schedule results in CD4+ lymphopenia in a majority of patients that can result in OIs. Pneumocystis pneumonia prophylaxis should be considered for patients who develop sustained lymphopenia on TMZ. © 2004 by American Society of Clinical Oncology. |
| Keywords: | adult; controlled study; aged; aged, 80 and over; middle aged; retrospective studies; major clinical study; thalidomide; neutropenia; cancer combination chemotherapy; alpha interferon; temozolomide; t lymphocyte; dacarbazine; low drug dose; melanoma; infection; thrombocytopenia; proportional hazards models; drug administration schedule; alkylating agent; pneumocystis pneumonia; drug effect; retrospective study; lymphocytopenia; immunology; proportional hazards model; chemically induced disorder; cd4+ t lymphocyte; cd4-positive t-lymphocytes; antineoplastic agents, alkylating; drug derivative; multivariate analysis; drug administration; lymphocyte; lymphopenia; lung aspergillosis; opportunistic infections; opportunistic infection; humans; human; male; female; priority journal; article |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 22 |
| Issue: | 4 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2004-02-15 |
| Start Page: | 610 |
| End Page: | 616 |
| Language: | English |
| DOI: | 10.1200/jco.2004.07.060 |
| PROVIDER: | scopus |
| PUBMED: | 14726505 |
| DOI/URL: | |
| Notes: | J. Clin. Oncol. -- Cited By (since 1996):148 -- Export Date: 16 June 2014 -- CODEN: JCOND -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work