Sorafenib and dacarbazine as first-line therapy for advanced melanoma: phase I and open-label phase II studies.

METHOD: The safety of oral sorafenib up to a maximum protocol-specified dose combined with dacarbazine in patients with metastatic, histologically confirmed melanoma was investigated in a phase I dose-escalation study and the activity of the combination was explored in an open-label phase II study. RESULTS: In the phase I study, three patients were treated with sorafenib 200 mg twice daily (b.i.d.) plus 1000 mg m(-2) dacarbazine on day 1 of a 21-day cycle and 15 patients had the sorafenib dose escalated to 400 mg b.i.d. without reaching the maximum tolerated dose of the combination. In the phase II study (n=83), the overall response rate was 12% (95% CI: 6, 21): one complete and nine partial, with median response duration of 46.7 weeks. Stable disease was the best response in 37%; median duration was 13.3 weeks. Median overall survival (OS) was 37.0 weeks (95% CI: 33.9, 46.0). CONCLUSION: Oral sorafenib combined with dacarbazine had acceptable toxicity and some antineoplastic activity against metastatic melanoma.

Patient-selected dosing in a six-month open-label study evaluating oral sumatriptan in the acute treatment of migraine. Sumatriptan Tablets S2CM10 Study Group.

BACKGROUND: Dosing recommendations for oral sumatriptan as acute treatment for migraine have ranged from 25 mg to 100 mg. Patient dose preferences have not been studied in a setting mimicking clinical practice. METHODS: In an open-label study evaluating patient acceptance and the relative efficacy and safety of 25 mg, 50 mg, and 100 mg doses of oral sumatriptan over a period of six months, 338 patients treated three migraine attacks with 50 mg sumatriptan and then were allowed to double or halve the dose. After treating another three attacks, they were again allowed to adjust the dose by one level. RESULTS: After migraine attack 3, 37% of patients chose to continue with the 50 mg dose, 50% increased the dose to 100 mg, and 12% decreased it to 25 mg. After attack 6, 8%, 33%, and 58% of patients chose the 25 mg, 50 mg, and 100 mg doses, respectively; only 3% of those taking the 100 mg dose chose to reduce it. Overall, the mean percentages of attacks per patient in which headache relief had been obtained 4 h after dosing were 71%, 71%, and 80% for the 25 mg, 50 mg, and 100 mg doses, respectively. Patients who decreased the dose to 25 mg after attack 3 experienced decreases both in adverse events and percentage of attacks with headache relief, whereas in those who increased the dose to 100 mg, likelihood of headache relief increased but the incidence of adverse events did not. CONCLUSIONS: More patients chose the 50 mg or 100 mg dose than the 25 mg dose. All three doses had similar efficacy and tolerability.

Efficacy and safety of sumatriptan tablets (25 mg, 50 mg, and 100 mg) in the acute treatment of migraine: defining the optimum doses of oral sumatriptan.

That sumatriptan tablets are effective and well tolerated in the acute treatment of migraine has been established, but the relationship between dose and efficacy has not been adequately defined to date in clinical trials. This multinational double-blind trial (N = 1003) in which patients treated up to three migraine attacks with sumatriptan 25 mg, 50 mg, 100 mg, or placebo, with a second independently randomized dose for headache recurrence, evaluated the efficacy and tolerability of three doses of sumatriptan. The results demonstrate that all doses of sumatriptan were superior (P < 0.05) to placebo in reducing moderate or severe predose headache to mild or no headache 4 hours postdose for each of the three treated attacks; sumatriptan 50 mg and 100 mg were each superior (P < 0.05) to sumatriptan 25 mg 4 hours postdose for two of three attacks. Sumatriptan (all doses) was similarly effective at relieving nausea and photophobia or phonophobia or both and at reducing clinical disability. Headache recurrence was experienced by similar proportions of patients across treatment groups (35% to 48% after placebo; 26% to 39% after sumatriptan). Relief of recurrent headache 2 hours after the second dose of study medication occurred in greater percentages of patients using any dose of sumatriptan compared with patients using placebo to treat recurrence. The incidence of adverse events with 25-mg and 50-mg sumatriptan tablets was similar to the incidence with placebo and lower than the incidence with 100-mg sumatriptan tablets. These data provide the first demonstration from a large well-controlled clinical trial that both the 50- and 100-mg doses are more effective than the 25-mg dose and that the 50-mg dose is associated with a lower incidence of adverse events than the 100-mg dose.

Let's talk: the effect of maternal hearing status on interactions with toddlers who are deaf.

Eight dyads comprised of deaf toddlers and their deaf mothers (D-D dyads) and eight dyads in which only the toddlers were deaf (D-H dyads) were compared on the use and success of various means for establishing mutual attention for communication. Three different sequences of invitation and response resulting in mutual attention for communication were examined. Results indicated that for two of the types of invitation, the D-D dyads experienced significantly more episodes of mutual attention, not only because the deaf mothers were more active, but also because their deaf toddlers were more responsive. The relevance of these differences for development and for communication was explored, and implications were discussed for early intervention with D-H dyads.