Phase II trial of high-dose cisplatin with sodium thiosulfate nephroprotection in patients with advanced carcinoma of the uterine cervix previously untreated with chemotherapy.

Cisplatin is one of the most active single agents in the treatment of advanced cancer of the cervix. The concurrent administration of the nephroprotective agent, sodium thiosulfate, has enabled exploitation of the therapeutic potential of cisplatin. To explore the role of cisplatin dose intensity in the treatment of patients with cancer of the uterine cervix, patients with persistent/recurrent measurable disease were treated with cisplatin at 200 mg/m2 as a 2-hr infusion with sodium thiosulfate given at 3.3 g/m2 1 hr prior to cisplatin and 6.6 g/m2 during the cisplatin infusion. Treatment was repeated monthly. Due to the known cumulative toxicity of cisplatin, treatment beyond two cycles (400 mg/m2) was given only to those patients who had at least demonstrated a PR. Audiologic evaluation was done prior to each cycle of treatment. Eleven patients were entered with a median age of 43 years (range, 25-57), a median KPS of 80% (range, 60-90%), and nine epidermoid and two adenocarcinoma, and all patients had received previous pelvic irradiation. Twenty-eight cycles of treatment were given: 1, five cycles; 3, three cycles; 7, two cycles. No greater than or equal to 3+ hematologic, neurologic, or renal toxicity was demonstrated. Ototoxicity was demonstrated in the mild to moderate hearing loss range (3000-8000 Hz). The greatest threshold shift occurred after the first course of cisplatin. There were three PRs with a maximum duration of 4 months. Due to the significant toxicities encountered, the low response rate, and the limited duration of responses, this trial was closed early to accrual.     

“Salvage chemotherapy” of malignant disease: importance of precisely defining the goals of treatment

Journal of Cancer Research and Clinical Oncology -     

Noise in polymer gel measurements using MRI

With the development of conformal radiotherapy, particularly intensity modulated radiation therapy (IMRT), there is a clear need for multidimensional dosimeters. A commercial polymerizing gel, BANG-2 gel (MGS Research, Inc., Guilford, CT), has recently been developed that shows potential as a multi-dimensional dosimeter. This study investigates and characterizes the noise and magnetic resonance (MR) artifacts from imaging BANG-2 gels. Seven cylindrical vials (4 cm diam, 20 cm length) were irradiated end on in a water bath and read using MRI (B0=1.5 T, TE=20 ms/100 ms, TR=3000 ms). The gel calibration compared the measured depth-dose distributions in water against the change in solvent-proton R2 relaxivity of the gel. A larger vial (13 cm diam, 14 cm length) was also irradiated to test the calibration accuracy in a vial of sufficient volume for dose distribution measurements. The calibration curve proved accurate to within 1.3% in determining the depth dose measured by the larger vial. An investigation of the voxel-to-voxel (IXIX 3 mm3) noise and sensitivity response curve showed that the voxel-to-voxel variation dominated the dose measurement uncertainty. The voxel-to-voxel standard deviation ranged from 0.2 Gy for the unirradiated gel to 0.7 Gy at 20 Gy. Slice-to-slice R2 magnitude deviations were also observed corresponding to 0.2 Gy. These variations limited the overall accuracy of the gel dose measurements and warrant an investigation of more accurate MR readout sequences.     

Thermal regulatory responses to submaximal cycling following lower-body cooling in humans

This study compared the effects of pre-exercise cooling with control water immersions on exercise-induced thermal loads derived from steady-state submaximal exercise. Eight healthy male participants [mean (SEM) age 29 (1) years, maximal oxygen uptake 3.81 (0.74) l·min^–1, and body surface area 1.85 (0.11) m²] took part in experiments that included 30 min of baseline data collection [ambient temperature 21.3 (0.2°C)], 30 min of immersion in water to the level of the supra-iliac crest [water temperatures of 35.1 (0.3)°C for thermoneutral and 17.7 (0.5)°C for precooled treatments], and 60 min of cycling exercise at 60% of maximal oxygen uptake. No significant differences were noted during exercise in net mechanical efficiency, metabolic rate, O₂ pulse, or ratings of perceived exertion between the two treatments. Precooling resulted in a significant negative body heat storage during immersion and allowed greater heat storage during exercise. However, net body heat storage for the entire protocol was no different between treatments. Cooling significantly lowered rectal, mean skin, and mean body temperatures as well as more than doubling the exercise time until a 0.5°C rectal temperature increase was observed. The cooling trial significantly delayed onset of sweating by 19.62 min and decreased sweat rate by 255 ml·h^–1 compared to control. Thermal and sweat sensation scores were lower after the cooling treatment compared to control. These data suggest that lower-body precooling is effective at decreasing body heat storage prior to exercise and decreases reliance on heat dissipation mechanisms during exercise. Therefore, this unique, well-tolerated cooling treatment should have a broader application than other precooling treatments. Electronic Publication     

Cardiotoxicity of Antineoplastic Agents: What Is the Present and Future Role for Imaging?

As antineoplastic treatment options expand at an increasing rate, both traditional and novel agents continue to be limited by their cardiotoxic effects. While functional decline becomes clinically apparent at late states of toxicity, little is known about early stages during which treatment or prevention may still be an option. Several imaging modalities, including echocardiography, multiple gated acquisition, and cardiac magnetic resonance imaging have the ability to identify cardiac effects before they produce clinical symptoms. Here we discuss the current and future role of cardiac imaging in the assessment of cardiotoxicity of antineoplastic agents.