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139 Background: DN given q4w has shown superiority in delaying skeletal related events over q4w zoledronic acid (ZA). Recently it has been demonstrated that ZA q12w is non-inferior to ZA q4w. The objective of REDUSE is to show non-inferiority for DN q12w versus q4w in terms of SSE. Here we present an interim analysis for the secondary endpoint HC. Methods: Patients (pts) with castration resistant prostate cancer (planned N=690) were randomized 1:1 to DN q4w (Arm A) vs q12w (Arm B) after a 16 week induction phase with application q4w. All pts received vitamin D (ViD) 400 U and calcium (Ca) 500 mg daily. Measurement of corrected serum-Ca was mandatory before each DN injection. This interim analysis was performed after 3.5 years of accrual. Men who received ≥ 1 dose of DN were considered evaluable. Results: 383 pts were evaluable. HC occurred in 28.7% during the first 16 weeks (DN q4w for all pts) and 30.2% afterwards. After the induction phase HC occurred in 40.2% in Arm A and in 20.3% in Arm B. Grade 3 (2.1%) and 4 (1.1%) HC were rare, most frequently occurring in the first 16 weeks. After 1 year of treatment, the incidence of HC was lower in both arms (A: 30.8%, B: 18.7%). A clinically relevant difference for HC was noted between the two arms after the induction phase (table). Conclusions: In our trial nearly 30% of all men treated with DN experienced HC in the q4w induction phase despite mandatory supplementation of calcium and ViD and measurement of Ca. This rate was considerably higher than reported in the registration trials of DN (13%). After induction treatment the incidence of HC is considerably lower in the q12w arm compared to q4w. This suggests that DN given q12w has a more favorable long time toxicity profile (HC) compared to DN q4w. Change in HC grade after week 16 (week 1 – 12: DN q4w Arm A+B), thereafter q4w in Arm A and q12w in Arm B. Clinical trial information: NCT02051218. [Table: see text]

TPS5086Background: The current first-line treatment for patients with CRPC and disease progression is either treatment with abiraterone acetate/prednisone, ENZ, or treatment with docetaxel in more ...

The originally Greek principle of “primum non nocere” (“first, do no harm”) is said to have been translated into Latin by Scribonius Largus, the private physician of the emperor Tiberius Claudius. Scribonius Largus apparently recommended this strategy to his colleagues to improve the image of Roman medics, who at the time had a reputation as poisoners. In the context of the editorial recently published in Journal of Clinical Oncology, “Active Surveillance for Clinical Stage I Testicular Cancer,”1 this statement probably means that you should not harm a patient by giving adjuvant treatment. As a profession, we have made some progress since the time of Scribonius Largus (approximately 50 AD). However, the case vignette presented by Vaughn1 in his editorial illustrates that despite our best intentions, we may expose individual patients to even greater harm by trying to avoid harm. Most physicians would agree in retrospect that despite the attempt to avoid adverse effects of adjuvant treatment, the patient presented was eventually exposed to even greater toxicity with intensive combination chemotherapy.

10500 Background: Standard first-line treatment of locally advanced/metastatic soft tissue sarcoma (STS) is Dox. GemDoc has activity in STS and is used in relapsed STS after failure of at least one...

4588 Background: Everolimus is a potent, orally bioavailable inhibitor of the mammalian target of rapamycin (mTOR) pathway and has shown activity in preclinical cancer models. This phase II study i...

4666 Background: No standard treatment options exist for pts with mCRPC who progressed during or shortly after docetaxel (doc) therapy. The epidermal growth factor receptor (EGFR) is overexpressed ...

5564 Background: In a previous study, we noted a response rate (RR) of 61% for the 3 drug combination of carboplatin, epirubicin and capecitabine in platinum-sensitive recurrent EOC. This combination however resulted in excessive grade (G) 3–4 haematological toxicity (55%) (BJC 2006; 94:74). The current trial therefore assessed the feasibility and efficacy of the 2 drugs, carboplatin and capecitabine as second- or third-line treatment. Methods: Pts were administered carboplatin (AUC5) day 1 and capecitabine at a starting dose of 750 mg/m2 bd, days 1–21, q21 (dose level 1). The capecitabine dose was deescalated to 625 mg/m2 (dose level -1) and 500 mg/m2 (dose level -2) according to toxicity. Pts with an objective response or stable disease received maintenance capecitabine (at the same dose level) for up to 12 months or until progression. Responses were assessed with RECIST criteria and CA-125. Results: 19 of the 20 pts enrolled were evaluable for toxicity and response. Dose-limiting toxicity was observed at dose level 1 (G3 fatigue, G3 diarrhoea, G3 neutropenia of > 14 days; n = 3/5), dose level -1 (G3 angina (n = 2), G3 vomiting, G3 palmar plantar erythema; n = 4/7) and dose level-2 (diarrhoea / fatigue; n = 1/7). One patient had a G3 carboplatin hypersensivity reaction. 8 pts received maintenance capecitabine which was well tolerated. The overall RR was 53% with 10 partial responses and 5 stable diseases. The median progression free survival (PFS) was 6.5 months (m) and the 6mPFS was 63% with 2 pts currently ongoing treatment. The median PFS on maintenance was 3.2 m. Conclusions: The combination was well tolerated at the recommended phase II dose of carboplatin (AUC 5) and capecitabine (500 mg/m2 bd) with partial responses in over half of the cases. [Table: see text]