Thomé, Stephan D.

e15031 Background: Two web based prognostic calculators, Adjuvant! and Numeracy (JCO 22:1797–1806, 2004) are widely used to provide individual patient outcome predictions to aid decisions regarding adjuvant therapy for colon cancer. The comparability of these tools has not been studied yet. The aim of this project was to assess whether the Numeracy and Adjuvant! Colon cancer prognostic tools produced similar results for patients with resected stage II and III colon cancer based on a set of hypothetical patients. Methods: All possible hypothetical scenarios were formulated for the Numeracy calculator based on all potential combinations of age, lymph nodes status, tumor stage, and grade of tumor. These were applied to three post- surgical therapy choices: observation, 5-FU (5-fluorouracil), or FOLFOX (5-FU, leucovorin and oxaliplatin). Predictions for these hypothetical scenarios (N= 192 for males and 192 for females) were also entered into the Adjuvant! Program. Predicted relapse free survival (RFS) and overall survival (OS) were obtained using both calculators. Wilcoxon signed rank tests were used to compare the numerical predictions between the calculators for each outcome. Results: In the majority of the 384 hypothetical patient scenarios, predictions for RFS and OS from Adjuvant! were statistically significantly higher than from Numeracy (p value < 0.05), except for age≥70 for FOLFOX, and the number of positive nodes of 0 and 1–4 using FOLFOX, among males. The net estimate of benefit for RFS and OS for 5-FU over surgery, obtained from Adjuvant! and Numeracy, were similar (for both males and females), but the benefit in RFS and OS for FOLFOX over 5-FU obtained from Adjuvant! was significantly lower than the estimate obtained from Numeracy (p value < 0.05). Conclusions: Based on a hypothetical set of patients with resected stage II and III colon cancer, the estimated benefit in RFS and OS of FOLFOX over 5-FU based chemotherapy is lower in Adjuvant! than in the Numeracy tool (but benefit for 5-FU over surgery alone is similar). Further studies are needed to clarify the discrepancy and to assess which of these tools most accurately reflects actual patient outcome. No significant financial relationships to disclose.

e24086 Background: Nasal vestibulitis has been infrequently described as a side effect of cancer-directed therapy; however, a preliminary study reported that 71% of patients undergoing taxane chemotherapy experienced nasal vestibulitis symptoms. This natural history trial describes the incidence, characteristics, and severity of nasal vestibulitis symptoms among patients undergoing paclitaxel, docetaxel, and non-taxane chemotherapy. Methods: Eligible participants who reported baseline (prior to starting chemotherapy) nasal symptoms ≤ 2 on a 10-point scale were enrolled in this trial upon initiation of a new treatment regimen, involving paclitaxel or docetaxel, or non-taxane chemotherapy. Participants completed nasal symptom logs each time they received a dose of therapy until either the regimen was stopped or four months had passed. The proportion of patients reporting new nasal symptoms was estimated within each cohort with the 95% exact confidence interval (CI). A cumulative incidence model was utilized to quantify the incidence of treatment-emergent nasal symptoms within each cohort, while controlling for age, sex, smoking history, and history of asthma or allergies. Results: Thirty-five participants received paclitaxel, 21 received docetaxel, and 25 received other types of chemotherapy. 86.4% of participants were female, mean age was 60.2 ± 11.2 years; 93.8% of participants completed 2 or more surveys. A higher percentage of participants in the paclitaxel cohort experienced new nasal vestibulitis symptoms than participants in the other two cohorts. The percentage (95% CI) of participants with nasal symptoms, for patients receiving paclitaxel, docetaxel, and non-taxane chemotherapy were 74.3% (56.7%, 87.5%), 47.6% (25.7%, 70.2%), and 44.0% (24.4%, 65.1%), respectively. Epistaxis was reported by 60% of participants in the paclitaxel cohort. Paclitaxel-receiving participants also reported nasal dryness (48.6%), scabbing (40.0%), and pain (20.0%). Nearly half of participants reported moderate symptoms (4-7 out of a 10-point scale), with 8.6% reporting symptoms as severe (8-10 on a 10-point scale). Conclusions: Nasal vestibulitis is a common side effect of chemotherapy, especially paclitaxel chemotherapy.

1071 Background: N0234 is a phase II trial of gemcitabine at 1000 mg/m2 days 1 and 8 of a 21 day cycle and erlotinib at 150 mg daily in patients with previous therapy with either an anthracycline or a taxane for MBC. A partial response (PR) rate of 17% has been reported (ASCO 2005). Recent information suggests that over-expression of the EGFR pathway is frequent in patients with TNeg MBC. Methods: Tissue and serum were obtained for translational studies of ER, PR, HER2, and proteins related to EGFR pathway on tissue using immunohistochemistry; CK19, mammoglobin, and TTK on circulating tumor cells (CTCs). Markers were evaluated centrally, blinded to patient outcome. Complete data were available in 57 of 59 eligible patients; 20/57 patients (pts) were TNeg. Results: A PR rate of 25% and clinical benefit rate (PR + stable disease > 6 months)of 25% was observed in TNeg pts as compared to a PR rate of 14% (p = 0.30) and clinical benefit rate 22% (p= 0.75) for non-TNeg pts. Median progression free survival 72 days vs 98 days (p=0.13) and overall survival 227 days vs 738 days (p<0.001) were shorter for TNeg pts. Translational results for the EGFR pathway proteins and CTC analysis is forthcoming. Conclusions: The combination of gemcitabine and erlotinib appears to be as active in the non-TNeg and TNeg subset of patients on this trial. TNeg patients had an inferior clinical result, confirming the poor outcome seen in these patients. Data for the remaining biomarkers potentially predictive of activity will be presented. Supported by CA-25224, CA-37404. [Table: see text]

PURPOSE: Physicians and patients require quantitative information on the expected benefits of adjuvant therapy for primary breast cancer to make appropriate treatment decisions. To date, there has not been any widely available method for estimating the benefits from adjuvant systemic therapy, in terms of long-term disease-free survival probabilities, in patients with primary breast cancer. METHODS: Baseline prognostic information for primary breast cancer patients was estimated by asking 11 breast cancer specialists to complete a questionnaire on baseline prognosis and then using mean values. Data on the relative benefits of adjuvant therapy were culled from systematic reviews and randomized controlled trials. A computer algorithm was developed to calculate 10-year absolute outcome data. Results from this evaluation were compared with a previously described actuarial algorithm. RESULTS: Individual prognostic estimates varied within a group of breast cancer specialists, but mean values of their estimates closely followed published data. Translation of expected benefits of adjuvant therapy from relative to absolute terms was performed with a simple computer algorithm. The data were translated into tabular forms to facilitate user-friendly clinical use. CONCLUSION: The provided data should facilitate a better understanding of the absolute magnitude of benefit for available systemic adjuvant therapies in individual women with primary breast cancer. This should allow patients to make more informed decisions about their options.

Purpose Although it is well-established that fluorouracil- (FU-) based adjuvant therapy improves survival for patients with resected high-risk colon cancer, the magnitude of adjuvant therapy benefit across specific subgroups and for individual patients has been uncertain. Patients and Methods Using a pooled data set of 3,302 patients with stage II and III colon cancer from seven randomized trials comparing FU + leucovorin or FU + levamisole to surgery alone, we performed an analysis based on a Cox proportional hazards regression model. Treatment, age, sex, tumor location, T stage, nodal status, and grade were tested for both prognostic and predictive significance. Model derived estimates of 5-year disease-free survival and overall survival (OS) for surgery alone and surgery plus FU-based therapy were calculated for a range of patient subsets. Results Nodal status, T stage, and grade were the only prognostic factors independently significant for both disease-free survival and OS. Age was significant only for OS. In a multivariate analysis, adjuvant therapy showed a beneficial treatment effect across all subsets. Treatment benefits were consistent across sex, location, age, T-stage, and grade. A significant stage by treatment interaction was present, with treatment benefiting stage III patients to a greater degree than stage II patients. Conclusion Patients with high-risk resected colon cancer obtain benefit from FU-based therapy across subsets of age, sex, location, T stage, nodal status, and grade. Model estimates of survival stratified by T stage, nodal status, grade, and age are available at http://www.mayoclinic.com/calcs . This information may improve patients' and physicians' understanding of the potential benefits of adjuvant therapy.