Paclitaxel in older women with breast cancer. Combined analysis of CALGB 9342 and 9840 with a focus on age.
Authors: Lichtman SM , Hurria A , Cirrincione CT , Seidman AD , Winer E , Hudis C , Cohen HJ , Muss HB 
Published: December 2010

Abstract #6112

Older women with breast cancer are increasingly being treated with chemotherapy in both the adjuvant and metastatic settings. There is often concern about the side effects of chemotherapy in older adults. Paclitaxel is a common component of many regimens and the pharmacokinetics vary by age (Lichtman et al, JCO 2006). We combined data from two CALGB phase III treatment studies, both of which used paclitaxel to treat metastatic breast cancer, to assess the relationship of patient age with paclitaxel efficacy and toxicity. CALGB 9840 (Seidman, et al. JCO 2008) evaluated weekly paclitaxel (80 mg/m2 over 1 hour) vs. paclitaxel every 3 weeks (175 mg/m2 over 3 hours); CALGB 9342 (Winer, et al. JCO 2004) evaluated three doses of paclitaxel: 175 mg/m2, 210 mg/m2, or 250 mg/m2-each administered as a 3-hour infusion every 3 weeks. Patients were allowed a maximum of one prior chemotherapy regimen for metastases. Of a sample size 1048 patients (599 first line-57%; 449 second line-43%) we categorized patient age as (1) &lt;55 yrs (n=470; 45%); (2) 55-64 yrs (n=306; 29 %); (3) &gt;65 yrs (n=272; 26%). The median number of treatment cycles was similar across age categories within first line (9-10) and within second line (6-7) patients. Likelihood of response did not differ by age group either alone, after controlling for line of therapy, or after controlling for ER status, number of sites of metastatic disease, or BMI (p=0.13) . First line therapy (p=0.0001) and better performance score (p=0.0045) were significantly related to higher likelihood of response. After adjusting for line of therapy and several standard prognostic variables, age did not significantly relate to OS (p=0.66). First line therapy (p&lt;0.0001), better performance score (p&lt;0.0001), ER+ status (p&lt;0.0001), fewer number of metastatic sites (p=0.0026) and lower BMI (p=0.023) were significantly related to longer survival. The incidence of grades ≥ 3 toxicities that increased linearly with age category were: leucopenia (p=0.0099), granulocytopenia (p=0.022), anorexia (p-0.028), bilirubin elevation (p=0.0035), and neurotoxicity [neurosensory (p=0.00062); neuromotor (p=0.0002)]. There was no relationship between the incidence of severe infection and age. Of the toxicities listed above, only time to onset of grade &gt; 3 neurosensory/motor toxicity differed by patient age. Patients aged 65 or older experienced the shortest time to onset compared to younger patients (P=0.0014). This combined analysis demonstrates that older women with breast cancer derive similar efficacy from treatment with single-agent paclitaxel as younger women; however, older women are at increased risk for side effects, in particular myelosuppression, neurotoxicity, hyperbilirubinemia, and anorexia. Careful attention to these side effects in older adults is warranted. In particular, the time to onset of neurotoxicity is accelerated in older adults. Research is needed to determine whether this increased toxicity results in functional decline, increased risk of falls, or other adverse sequelae.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6112.