Mattar, B.

9587 Background: CIPN is characterized by adjectives not covered directly by most common measures of pain and functional limitations. Possible descriptors include numbness, tingling and shooting/burning pain. A prospective neuropathy treatment trial provided data to explore the relationship between self-reported aspects of this symptom. Methods: Baseline EORTC QLQ CIPN20 data and NCI CTCAE V3.0 (CTC)neuropathy grade (I-IV) were provided for all patients on trial. Spearman correlation coefficients and Kappa's coefficients of agreement were calculated between individual items and subscales of the CIPN20 as well as the CTC neuropathy scale. Simple regression models were applied to examine the association between the sensory symptoms and motor function in the fingers/hands (F/H). 200 patients provided 80% power to detect a correlation coefficient of 0.20 with a 5% Type I error. Results: A majority of patients reported “quite a bit” to “very much” numbness (57%) or tingling (62%) in F/H compared to “a little” or “not at all” (numbness (43%), tingling (38%)) by the CIPN20. In contrast, only 13% of the participants had grade III/IV neuropathy determined by the CTC scale. Fewer patients reported the higher two levels of CIPN20-measured shooting/burning pain in F/H (20% “quite a bit” to “very much”). Numbness and tingling were highly correlated (kappa=0.56), while neither were in high agreement with shooting/burning pain (kappa= 0.05 (tingling) and 0.14 (numbness)). The CIPN20 sensory and motor subscales were significantly associated with each other (p<.0001) but were not or only weakly associated with the CTC. Specifically, tingling, numbness, and shooting/burning pain were not associated with the CTC (R=0.16, 0.18 and 0 .11, respectively). Using the CIPN20, all three sensations; numbness, tingling and shooting or burning pain were strongly associated with motor function. Conclusions: The most common moderate to severe CIPN symptoms were numbness and tingling with shooting/burning pain being less common. Shooting/ burning pain appears to be a separate symptom experience from numbness and tingling. The CTC neuropathy grading scale appears to be less sensitive than the CIPN20 in picking up sensory symptoms. No significant financial relationships to disclose.

9531 Background: Chemotherapy induced peripheral neuropathy (CIPN) is a prevalent dose limiting toxicity for several important cancer treatment agents. CIPN can impair function and cause distress. There are no proven pharmacologic treatments for established CIPN currently. This double blind randomized placebo controlled trial evaluated a compounded topical gel for this problem. The novelty of this treatment is that it might incorporate several agents with different mechanisms of action to provide relief locally without negative systemic effects. Methods: Patients with CIPN (rated ≥4 out of 10) for at least one month, related to previous and/or concurrent exposure to neurotoxic agents, were randomized to baclofen 10 mg, amitriptyline HCL 40 mg and ketamine 20 mg in a pluronic lecithin organogel (BAK-PLO) vs placebo (PLO) to determine its effect on numbness, tingling, pain, and motor function. Exclusion criteria included other causes and/or current treatment for peripheral neuropathy. The primary endpoint was the baseline adjusted sensory subscale of the EORTC QLQ-CIPN20, at 4 weeks. Results: Between February and May 2008, 208 patients were enrolled onto this trial. Four week data are shown in the table below, higher numbers being better. The percentage of patients that had improvements of at least 10, on a 100 point scale, in the motor subscale was statistically significantly higher in the BAK-PLO arm, p=.04. There were no unwanted toxicities associated with the BAK-PLO that were significantly different from placebo and no evidence of CNS or systemic toxicity. Conclusions: Topical treatment with BAK-PLO appears to moderately improve symptoms of CIPN. This topical gel was well tolerated without systemic side effects. [Table: see text] No significant financial relationships to disclose.

623 Background: Neoadjuvant therapy plays an important role in breast cancer treatment. Unlike patients who undergo surgery followed by adjuvant therapy,there are no established guidelines for surgical management following neoadjuvant therapy. Methods: Surgical practice patterns from 50 patients in N0338 “Phase II trial of Docetaxel and Carboplatin administered every two weeks as induction therapy for Stage II and Stage III breast cancer” were reviewed. The protocol did not mandate surgical therapy leaving the decision to the treating surgeon and patient. Results: 66% of patients underwent mastectomy (M) and 33% underwent breast conservation therapy (BCT). Three (9%) had immediate reconstruction. Eight (24%) underwent contralateral prophylactic M. Residual tumor size did not always impact primary surgical therapy. In the M group 4 (12%) had no residual disease, 15 (45%) < 2cm and 14 (42%) > 2cm; whereas, in the BCT group 1 (6%) had no residual disease, 12 (70%) < 2cm and 4 (24%) > 2cm. Axillary lymph node (ALN) staging varied tremendously. Three (6%) patients presented with palpable lymphadenopathy and proceeded to complete axillary lymph node dissection (ALND) after chemotherapy (CT). Fine needle aspiration (8) or core needle biopsy (7) of the axilla was performed in 15 (30%) patients before CT; 1 was negative and went on to have sentinel lymph node biopsy (SLNB) after CT; 14 (94%) were positive with 13 (86%) going on to ALND and 1 SLNB after CT. Five (10%) underwent SLNB prior to CT. One (20%) was positive and went on to have ALND after CT; 4 (8%) were negative and had no further ALN staging. A total of 19 (39%) had SLNB after neoadjuvant therapy; 13 (68%) were positive and underwent ALND; 1 SLNB failed; 2 of 5 that were negative underwent ALND with 1 having a positive lymph node. Ten (20%) underwent ALND with no pre-operative staging with 8 being positive for ALN metastases. Conclusions: Review of study data from multiple institutions revealed no consistent criteria in selection of surgical intervention for the breast tumor or ALN staging. There remains a need for further research in this area to establish standard practice guidelines. Support from NIH, sanofi-aventis, Amgen, Breast Cancer Research Foundation. No significant financial relationships to disclose.

Abstract Background: Postmenopausal women with significant osteopenia/osteoporosis are at increased risk of fracture, a risk that is exacerbated by the use of Aromatase Inhibitors (AIs). Bisphosphonates may be used for these patients because there is no known interaction with estrogen and/or progesterone receptors (ER, PR). This study evaluated the concurrent use of zoledronic acid in patients with significant osteopenia or osteoporosis who received initial adjuvant letrozole therapy for primary BC, to determine if further bone mineral density (BMD) loss could be prevented.Methods: Postmenopausal women with Stage I-IIIa, ER and/or PR + BC, no evidence of metastatic disease, and a BMD T-score &lt; -2.0 were treated with daily letrozole 2.5 mg/d, vitamin D 400 international units/d, calcium 500 mg twice daily, and 4 mg I.V. zoledronic acid every 6 months (for 5 years). The BMD was measured at baseline and at one year. Kruskall-Wallis p-value methodology was used as the method of statistical analysis. Since this was a single-arm study, the analysis plan was primarily descriptive. The primary endpoint was the mean change in lumbar spine (LS) BMD at 1 year.Results: 60 patients were enrolled; 46 completed 1 year of treatment. Mean patient age was 67 years, with 44% having taken prior tamoxifen. At 1 year (see figure 1), LS BMD increased 2.66% (p=0.01), femoral neck (FN) BMD increased 4.81% (p=0.01), and any measured endpoint (within the LS or FN) increased 4.55% (p=0.0052). 7% of patients experienced a fracture vs.13% with a pre-existing history of fracture before enrollment. No patients had disease recurrence during year 1. Toxicity was minimal with arthralgia as the most common complaint. There were no reports of osteonecrosis of the jaw.Conclusion: Zoledronic acid prevents additional bone loss in postmenopausal women with significant osteopenia or osteoporosis initiating letrozole. Treatment with zoledronic acid was associated with an improvement in BMD. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2103.