Psychologic and neuropsychologic functioning of patients with limited small-cell lung cancer treated with chemotherapy and radiation therapy with or without warfarin: a study by the Cancer and Leukemia Group B.

PURPOSE: The current study assessed the psychologic and neuropsychologic functioning of patients with small-cell lung cancer who were randomized in a large clinical trial to receive intensive doxorubicin, cyclophosphamide, etoposide (ACE)/cisplatin, cyclophosphamide, etoposide (PCE) chemotherapy and radiation therapy (RT) to the primary tumor and prophylactic whole-brain irradiation with (regimen I) or without (regimen II) warfarin. PATIENTS AND METHODS: Patients' emotional states and cognitive functioning were assessed using the Profile of Mood States (POMS) and Trail Making B Test (Trails B), respectively. Two hundred ninety-five patients completed the POMS and Trails B at pretreatment, 224 patients after the completion of the ACE course of chemotherapy (week 9), and 177 patients after the completion of the PCE chemotherapy and RT (week 17). RESULTS: No differences on the POMS or Trails B measures were found between the two treatment arms as predicted, given that the only difference between the two treatment arms was the presence or absence of warfarin. Analysis of the POMS revealed that, overall, mean scores remained stable over the course of treatment; however, women showed a trend toward higher mean scores, which indicated a higher level of distress, compared with men at the pretreatment assessment. Examination of cognitive functioning, measured by the Trails B, revealed improved performance from baseline to post-ACE chemotherapy, which is consistent with a practice effect, but a significant worsening of Trails B scores post-RT compared with the pre-RT assessments, which is consistent with impaired cognitive functioning because of treatment (P < .0001). CONCLUSION: Emotional state, measured by the POMS, did not differ between the groups or change significantly over time in this study of small-cell lung cancer patients treated with a combination of chemotherapy and RT plus or minus warfarin. However, the pattern of relatively stable POMS scores and poorer Trails B performance post-RT suggested that this combination of chemotherapy and RT had a negative impact on cognitive functioning.

Randomized trial of chemotherapy and radiation therapy with or without warfarin for limited-stage small-cell lung cancer: a Cancer and Leukemia Group B study.

PURPOSE: Studies by the Veterans Administration Cooperative Studies Program and Cancer and Leukemia Group B (CALGB) suggested that the addition of warfarin to chemotherapy might enhance response and/or survival in small-cell lung cancer (SCLC). This randomized study evaluated the effect of warfarin with chemotherapy and radiation therapy in limited-stage SCLC. PATIENTS AND METHODS: Patients were randomized to receive warfarin or no warfarin. All patients received three cycles of doxorubicin, cyclophosphamide, and etoposide (ACE). Cycles 4 and 5 (cisplatin, cyclophosphamide, and etoposide [PCE]) were given concurrently with radiation therapy. Three cycles of ACE were given after chemoradiation therapy, but were discontinued due to a high rate of pulmonary toxicity. RESULTS: There were no significant differences in response rates, survival, failure-free survival, disease-free survival, or patterns of relapse between the warfarin-treated and control groups. In patients treated according to the initial design, an increase in failure-free survival seen with warfarin treatment approached significance (P = .07). Preamendment results, while not significant, did not have superimposable treatment survival curves. A landmark analysis at 8 months showed a median survival time after the landmark for complete responders of 33 months with warfarin treatment compared with < or = 13.75 months for complete or partial responders not treated with warfarin (P = .05). Differences between the complete responders in this preamendment population were not significant (P = .103). CONCLUSION: Warfarin does not appear to improve outcome significantly in limited-stage SCLC. However, the differences in some variables between populations before the protocol amendment correspond to the favorable effects of anticoagulants observed in previous studies.