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High-quality response to multiple myeloma (MM) therapy can be predictive for improved outcomes. Novel agents may improve the depth of responses and therefore prolong survival. We report on the extended follow-up of a phase II study in frontline MM of bortezomib alone and in combination with dexamethasone. Forty-nine previously untreated, symptomatic MM patients received bortezomib 1.3 mg/m(2), days 1, 4, 8, 11, for up to six 3-week cycles. High-dose dexamethasone was added for patients not reaching either a partial response after cycle 2 or a complete response (CR) after cycle 4. The overall response rate in 48 evaluable patients was 90%, with 42% achieving at least a very good partial response, of which 19% were CR/near CR. Thirty-six patients received high-dose dexamethasone with 28 (77%) showing improved response. Twenty-seven patients have undergone successful stem-cell transplantation (SCT). After median follow-up of 49 months, 15 patients have died; median overall survival has still not been reached, with an estimated survival at 4 years of 67%. Overall survival with and without SCT was not different (P = 0.54). Grade 3/4 adverse events included neutropenia (10%), sensory neuropathy (6% grade 3), neuropathic pain (4% grade 3), and diarrhoea (4% grade 3). Bortezomib +/- dexamethasone is an effective and well-tolerated induction regimen for the frontline treatment of MM.

Purpose: Addition of either nab-paclitaxel or erlotinib to gemcitabine to treat advanced pancreatic cancer has demonstrated overall survival benefit. This study was conducted to evaluate the tolerability and safety of combining all three drugs and assess preliminary evidence of efficacy.Methods: In this open-label, phase 1b study, patients with previously untreated, advanced pancreatic cancer were treated in 28-day cycles with intravenous gemcitabine/nab-paclitaxel on days 1, 8, and 15, and once daily oral erlotinib. A standard "3 + 3" design was used. Dose level 1 (DL1) for gemcitabine (mg/m(2))/nab-paclitaxel (mg/m(2))/erlotinib (mg) was 1000/125/100, respectively, with de-escalation to DL-1 (1000/100/100), DL-2b (1000/75/100), and DL-3 (1000/75/75). The maximum tolerated dose (MTD) was defined by occurrence of dose-limiting toxicity (DLT) in ≤1 of six patients within the first cycle. Efficacy was assessed with CT scans performed at two-cycle intervals.Results: Nineteen patients were enrolled. DLTs occurred in two patients at DL1, three patients at DL-1, two patients at DL-2b, and one patient at DL-3. The MTD for the combination of gemcitabine/nab-paclitaxel/erlotinib was DL-3 (1000/75/75). In analyses of efficacy among 14 evaluable patients, partial responses were observed in four of six patients at DL1, one of two patients at DL-2b, and two of six patients at DL-3.Conclusion: The addition of erlotinib to gemcitabine and nab-paclitaxel is not tolerable at standard single-agent dosing of all drugs. However, significant clinical activity was noted, even at DL-3. Further study of the combination will need to incorporate reduced dosing. [ABSTRACT FROM AUTHOR]