A 12-month multicenter, randomized study comparing the levonorgestrel intrauterine system with the etonogestrel subdermal implant.

OBJECTIVE: To compare the levonorgestrel intrauterine system (LNG-IUS 8), which has an average levonorgestrel release rate of ∼8 µg/24 hours during the first year (total levonorgestrel content 13.5 mg; Jaydess/Skyla), with the etonogestrel (ENG) subdermal implant (total content, 68 mg) with regard to the 12-month discontinuation rate (primary outcome). DESIGN: Randomized, open-label, phase III study. SETTING: Thirty-eight centers in six European countries. PATIENT(S): Study population of 766 healthy nulliparous and parous women aged 18-35 years. INTERVENTION(S): The LNG-IUS 8 or the ENG implant. MAIN OUTCOME MEASURE(S): Discontinuation rate, by treatment group, at Month 12. RESULT(S): The 12-month discontinuation rates were 19.6% and 26.8% in the LNG-IUS 8 and ENG implant groups, respectively. The -7.2% difference was statistically significant (95% confidence interval -13.2%, -1.2%). Fewer women in the LNG-IUS 8 group than in the ENG implant group discontinued because of increased bleeding (3.2% vs. 11.3%) or adverse events (14.3% vs. 21.8%). At 12 months, more women in the LNG-IUS 8 group than in the ENG implant group were "very/somewhat satisfied" with their bleeding pattern (60.9% vs. 33.6%) and reported a preference to use their study treatment after study completion (70.1% vs. 58.5%). CONCLUSION(S): The LNG-IUS 8 was associated with a significantly lower 12-month discontinuation rate compared with the ENG implant; mainly because ENG implant users frequently discontinued due to increased bleeding. More LNG-IUS 8 users than ENG implant users reported being "very/somewhat satisfied" with their bleeding pattern, and reported a preference to continue using their study treatment after the study. CLINICAL TRIAL REGISTRATION NUMBER: NCT01397097.

Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer: A phase II trial.

BACKGROUND: The oral multikinase inhibitor regorafenib improves overall survival (OS) in patients with metastatic colorectal cancer (CRC) for which all standard treatments have failed. This study investigated regorafenib plus modified FOLFOX (mFOLFOX6) as first-line treatment of metastatic CRC. METHODS: In this single-arm, open-label, multicentre, phase II study, patients received mFOLFOX6 on days 1 and 15, and regorafenib 160 mg orally once daily on days 4-10 and 18-24 of each 28-day cycle. The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included disease control rate (DCR), OS, progression-free survival (PFS) and safety. RESULTS: Median overall treatment duration with any study drug was 9.9 months (range 0.6-19.6); median treatment duration with regorafenib was 7.7 months (range 0.1-19.5); six patients remained on regorafenib for more than 1 year. Fifty-three patients received at least one dose of regorafenib. ORR was 43.9% (all partial responses); DCR was 85.4%; median OS was not reached; median PFS was 8.5months. Treatment-emergent adverse events were experienced by all patients but were manageable with dose modifications. CONCLUSION: Regorafenib+mFOLFOX6 as first-line treatment in patients with metastatic CRC did not improve ORR over historical controls. Regorafenib plus mFOLFOX6 did not appear to be associated with a markedly worse tolerability profile versus mFOLFOX6 alone.

Effects of an ethinyl estradiol/gestodene transdermal contraceptive patch on the endometrium: a single-center, uncontrolled study.

AIM: This study aims to investigate the effect of a transdermal contraceptive patch containing ethinyl estradiol and gestodene on endometrial proliferation over 1 year. MATERIALS & METHODS: In this open-label, uncontrolled, Phase IIb study, women (aged 18-35 years) used the patch for 13 cycles of 28 days. The primary variable was histologic endometrial effects at cycle 13. Secondary objectives included contraceptive efficacy and safety. RESULTS: Overall, 89 women were treated. At all visits, endometrial biopsies were devoid of any abnormalities. One woman became pregnant. The patch was well tolerated, with no safety concerns. CONCLUSION: The ethinyl estradiol and gestodene patch had an endometrial effect consistent with suppression of endometrial proliferation in most patients. No endometrial abnormalities or other concerns were reported; compliance was good.