Phase dose schedules

TABLE 20.10. Design and Dosing Schedule for a First Repeat-Dose Phase I Study... 

Canertinib appears to have been evaluated in more phase I and II trials than the other inhibitors discussed in this review [84-87]. It has been studied under a wide variety of oral dosing schedules. Moreover, canertinib... 

In phase II studies with topotecan alone, there is cytotoxic activity in lung cancer with intermittent dose schedules (33), as well as in lung cancer patients with topoisomerase II refractory disease (34). In advanced head and neck cancer topotecan is well-tolerated and has single-agent activity similar to that of cisplatin, 5-fluorouracil, and methotrexate... 

Calvo E, Cortes J, Rodriguez J, Sureda M, Beltran C, ReboUo J, Martinez-Monge R, Berian JM, de Irala J, Brugarolas A. Fixed higher dose schedule of suramin plus hydrocortisone in patients with hormone refractory prostate carcinoma a multicenter Phase II study. Cancer 2001 92(9) 2435 3. 

Rubin E, Abbruzzese JL, Morrison BW, Mazina K, Lee Y. 2000. Phase I trial of the farnesyl protein transferase inhibitor L-778,123 on a 14- or 28-day dosing schedule. Proc. Am. Soc. Clin. Oncol. 19 718... 

Most often, for each drug, the lattice of dose schedules to explore is established in light of data from previously conducted Phase 1 trials. Several escalation schemes are encountered. For a two-drug combination one could escalate the doses of one drug while using fixed doses for the second one, or escalate both drugs either alternately or at the same time. 

Drug response is maximal during the absorption phase, is evident in 15 to 30 minutes, and lasts 2 to 6 hours. With immediate-release stimulants, most patients require a two or three times daily dosing schedule due to the short half-lives of these drugs (2 to 4 hours for methylphenidate and dexmethylphenidate and approximately 6 hours for dextroamphetamine). ... 

A description (e.g., in a table) of studies. Xia et al. (2011) provide an example of such a table. At a minimum, the table should include the planned Phase 2 and 3 studies. The description of studies includes study design (e.g., fixed versus flexible dose, parallel versus crossover), dosing schedule, study location, treatment groups and doses, number of subjects planned (by treatment group and doses), patient population (e.g., based on planned indication, special age groups), and duration of study. 

Two dosing schedules were studied dicing Phase I evaluation of MAG-CPT. An i.v. infusion over 30 min every 28 days [114], and as an alternative, daily treatment (x3) repeated every four weeks [115]. hi the first study [114] 62 patients were entered starting at a dose of 30 mg/m (camptothecin-equivalent). Dose escalation progressed to an MTD of 240 mg/m with 200 mg/m the recommended dose for further studies. At 240mg/m the DLTs included grade 4 neutropenia and thrombocytopenia, and grade 3 diarrhoea. Severe and impredictable cystitis was also seen. 

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