A phase I combination dose-escalation study of eribulin mesylate and gemcitabine in patients with advanced solid tumours: a study of the Princess Margaret Consortium.

BACKGROUND: Eribulin mesylate is a synthetic microtubule inhibitor that showed cytotoxic synergy in combination with gemcitabine preclinically. This combination was assessed in a Phase I dose-finding trial in patients diagnosed with advanced solid tumours who had received up to two prior chemotherapy regimens for metastatic disease (CP cohort). METHODS: Dose escalation was performed in a 3+3 design to identify the recommended phase II dose (RP2D). Two additional expansion cohorts in women with gynaecologic cancers at the RP2D (G), and further dose escalation of metastatic chemotherapy-naive patients (CN), were evaluated. RESULTS: 45 patients were treated: 21 (CP), 10 (G) and 14 (CN). The initial combination of eribulin and gemcitabine was administered on days 1, 8, and 15 of a 28-day cycle; however, due to 2 out of 6 dose-limiting haematological toxicities at the first dose level, a reduced dose-intense schedule was assessed. The RP2D was defined at 1.0 mg m(-2) eribulin and 1000 mg m(-2) gemcitabine day 1 and 8 q3 weeks. No other significant toxicities were observed in the G expansion cohort. Neutropenia prevented further dose escalation in the CN cohort. Objective responses were seen in all three cohorts - 2/21 (CP), 1/10 (G) and 2/14 (CN). CONCLUSIONS: The combination of eribulin and gemcitabine was well tolerated at the RP2D.

SU-E-J-115: Graticule for Verification of Treatment Position in Neutron Therapy.

PURPOSE: Until recently the treatment verification for patients undergoing fast neutron therapy at our facility was accomplished through a combination of neutron beam portal films aligned with a graticule mounted on an orthronormal x-ray tube. To eliminate uncertainty with respect to the relative positions of the x-ray graticule and the therapy beam, we have developed a graticule which is placed in the neutron beam itself. METHODS: For a graticule to be visible on the portal film, the attenuation of the neutron beam by the graticule landmarks must be significantly greater than that of the material in which the landmarks are mounted. Various materials, thicknesses, and mounting points were tried to gain the largest contrast between the graticule landmarks and the mounting material. RESULTS: The final design involved 2 inch steel pins of 0.125 inch diameter captured between two parallel plates of 0.25 inch thick clear acrylic plastic. The distance between the two acrylic plates was 1.625 inches, held together at the perimeter with acrylic sidewall spacers. This allowed the majority of length of the steel pins to be surrounded by air. The pins were set 1 cm apart and mounted at angles parallel to the divergence of the beam dependent on their position within the array. The entire steel pin and acrylic plate assembly was mounted on an acrylic accessory tray to allow for graticule alignment. CONCLUSION: Despite the inherent difficulties in attenuating fast neutrons, our simple graticule design produces the required difference of attenuation between the arrays of landmarks and the mounting material. The graticule successfully provides an in-beam frame of reference for patient portal verification.

Identifying reinforcers for persons with profound handicaps: staff opinion versus systematic assessment of preferences.

We evaluated a systematic means of determining stimulus preferences among seven profoundly handicapped persons. Preferences were determined by observing student approach responses to individual stimuli. Results indicated that there were differential stimulus preferences across the multiply handicapped participants. However, results of the systematic assessment did not coincide with the results of a more traditional, caregiver-opinion method of assessing student preferences. A second experiment was then conducted with five participants to evaluate whether stimuli that were assessed to consistently represent preferences would function as reinforcers in skill training programs. Results indicated that stimuli that were systematically assessed to represent student preferences typically functioned as reinforcers when applied contingently. However, preferred stimuli as reflected by caregiver opinion did not function as reinforcers unless those stimuli were also preferred on the systematic assessment. Results are discussed in terms of assisting profoundly handicapped persons by (a) improving the effectiveness of training programs by increasing the likelihood of using stimuli that have reinforcing value and (b) increasing the overall quality of life by providing preferred stimuli in the routine living environment.