Paclitaxel-associated acute pain syndrome (P-APS) and its association on the development of peripheral neuropathy: NCCTG trial N08C1.

9047 Background: Paclitaxel is well known to cause an acute pain syndrome that has been referred to as arthralgias and myalgias. It has been hypothesized that this pain might actually be neurologic in origin (Loprinzi et al; Cancer J 2007; 13:399-403). A recent prospective cohort study evaluating the natural history of this paclitaxel-associated acute pain syndrome supported an association (p=0.0017) between the degree of paclitaxel-associated acute pain severity and the subsequent development of peripheral sensory neuropathy (Loprinzi et al; JCO, in press). Methods: Adult patients receiving at least 175 mg/m2 of paclitaxel every three weeks, with concomitant carboplatin, participated in this study. Patients completed questionnaires for 7 days following each dose of paclitaxel. They were asked to judge, on each day, pain that was new and that they thought was related to chemotherapy (graded on a scale of 0 to 10 with 10 being worst). They also completed questionnaires (EORTC CIPN-20 instrument) to collect neuropathy data at the beginning of each weekly cycle of therapy and monthly after chemotherapy completion. Descriptive statistics were utilized for study endpoints. Results: Eighty-five patients were accrued. Eighty-eight percent experienced pain, most prominent in the hips and lower extremities, which peaked at day 4 after the first paclitaxel cycle. Subjects who experienced less acute pain (scores of 0-4) with the first paclitaxel cycle had less neuropathy over 18 weeks of treatment than did patients with 5-10 pain score severities (Table). Conclusions: The paclitaxel-associated acute pain syndrome is common and does appear to be associated with the development of peripheral neuropathy. EORTC CIPN-20 endpoint Mean decrease in CIPN severity for P-APS score 0-4 (versus 5-10)* P value** Autonomic subscale 7.8 0.007 Motor subscale 7.9 0.004 Sensory subscale 11.3 0.001 Numbness—feet 17.0 0.001 Burning/shooting pain—feet 11.5 0.02 Tingling—feet 13.7 0.02 Numbness—hands 16.0 0.002 Burning/shooting pain—hands 8.7 0.02 Tingling—hands 11.0 0.04 * On a 0-100 point scale. ** Mixed modeling p values adjusted for age and race.