Phase I/II trial of intravenous Doxil and whole abdomen hyperthermia in patients with refractory ovarian cancer.

OBJECTIVE: A phase I/II study of Doxil combined with whole abdomen hyperthermia was conducted in patients with refractory ovarian cancer. Liposomal doxorubicin combined with hyperthermia has been shown to increase both liposomal delivery and drug extravasation into tumour xenografts resulting in enhanced cytotoxic effects. PATIENTS AND METHODS: Thirty patients with either recurrent or persistent epithelial ovarian cancer were enrolled. All patients had either measurable or assessable disease. Patients received intravenous (IV) Doxil at a dose of 40 mg m-2 as a 1-h infusion followed by whole abdomen hyperthermia. The phase I portion of the study was performed to determine the maximal tolerated dose (MTD) of hyperthermia. Quality of life (QoL) was performed at baseline, prior to each cycle and every 3 months. Plasma pharmacokinetic studies were performed with the first cycle. RESULTS: Ten patients participated in the phase I portion of the study which demonstrated that the MTD of hyperthermia was 60 min after either average vaginal and rectal temperatures of 40 degrees C had been achieved or after 30 min of power application, whichever was shorter. All 30 patients were either paclitaxel and/or platinum resistant initially or developed resistant disease. The median number of prior chemotherapeutic regimens was three (range 2-8) and six patients had been previously treated with Doxil. There were three partial responses for a response rate of 10% (95% CI: [2%, 27%]) and eight patients (27%; 95% CI: [12%, 46%]) had disease stabilization. The median time to progression or death was 3.4 months (95% CI: [2.6, 5.2]) and the median survival was 10.8 months (95% CI: [8.8, 17.4]). Twelve patients (40%) experienced palmar-plantar erythrodysesthesia (PPE), but only four (13%) experienced grade 3-4 PPE toxicity. Doxil systemic exposure was higher in those with grade 3-4 PPE compared to those with no PPE. None of the patients had grade 3-4 thermal toxicity due to hyperthermia. QoL was not decreased in patients responding to therapy. CONCLUSIONS: Therapy with intravenous Doxil and whole abdomen hyperthermia for patients with platinum/paclitaxel resistant ovarian cancer is feasible and does not negatively impact quality of life.

Prospective assessment of quality of life in ovarian cancer patients receiving whole abdomen hyperthermia and liposomal doxorubicin.

PURPOSE: Prospective assessment of quality of life (QoL) in patients with refractory, residual or recurrent ovarian cancer receiving whole abdomen hyperthermia and intravenous liposomal doxorubicin chemotherapy. METHODS: Treatment consisted of six cycles of intravenous liposomal doxorubicin at 40 mg m2 followed by whole abdomen hyperthermia with each cycle delivered every 4 weeks. QoL assessment was performed at baseline, prior to each cycle of chemotherapy and every 3 months during follow-up using self-administered questionnaires. Global QoL was rated on a seven-point scale and specific domains of QoL, disease related symptoms and treatment related toxicity were rated on a four-point scale. RESULTS: Thirty-two patients were enrolled on the study and 129 QoL questionnaires were completed. Average age was 57.9 (range 45-76); nine patients had persistent and 23 recurrent disease. Ten patients completed six cycles of therapy. Three patients returned follow-up surveys. Subjects rated their overall QoL and health at baseline as above average with mean scores 5.10 (95% CI=4.62-5.58) and 4.66 (95% CI=4.23-5.08), respectively. No significant change in overall QoL was found between baseline and cycles 4-6 of therapy. Mean ratings of overall health and subject reported differences in QoL between cycles were not significantly changed during therapy. Limited follow-up data were available, but scores suggest possible improvement in QoL for patients completing all therapy. Subjects rated the greatest negative impact on QoL in areas of role functioning and social functioning, where the mean (SD) over all cycles was 2.00 (0.67) and 1.98 (0.70), respectively. For physical symptoms, fatigue and sleep disturbance had the most negative impact on QoL with means (SD) of 2.26 (0.62) and 1.91 (0.70). The moderate treatment related toxicity seen in this study did not significantly impact patients reported QoL. CONCLUSIONS: Patients with unfavourable ovarian cancer responding to intravenous liposomal doxorubicin and whole abdomen hyperthermia maintained above average QoL during therapy. Limited data on patients completing protocol therapy demonstrated possible improvement in QoL.

Prospective study of neuropsychologic testing and quality-of-life assessment of adults with primary malignant brain tumors.

PURPOSE: To identify the characteristics of adult patients with newly diagnosed primary brain tumors associated with identifiable deficits in neuropsychologic function to target interventions to improve function and quality of life (QOL). MATERIALS AND METHODS: Adult patients with newly diagnosed primary brain tumors and their caregivers were enrolled and underwent a battery of standardized neuropsychologic tests, allowing for qualitative and quantitative assessment and sensitive to the effects of the brain tumor, QOL, or caregiver stress. RESULTS: We enrolled 68 patients with no prior radiotherapy. Patients with left hemisphere tumors reported significantly more memory problems and depressive symptoms. They also exhibited poorer attention and were more distractible, with poorer verbal fluency and poorer verbal learning. Patients with glioblastoma multiforme demonstrated poorer psychomotor speed and visual tracking than patients with non-glioblastoma multiforme histologic features. Patients and caregivers perceived QOL in a similar fashion, with significant correlation between patient and caregiver on hope testing and general QOL on the Linear Analog Self-Assessment Scale. CONCLUSIONS: Patients with left hemisphere tumors and glioblastoma multiforme histologic features demonstrated testable differences in neuropsychologic function and QOL that may be amenable to improvement with medical therapy or tailored rehabilitation programs. Caregiver assessments can predict patient QOL, which may be useful in patients with declining status.

Computed axial tomography tandem and ovoids (CATTO) dosimetry: three-dimensional assessment of bladder and rectal doses.

The purpose of this work is to compare bladder and rectal dose rates in brachytherapy for carcinoma of the cervix using two different dosimetry systems: traditional orthogonal radiograph-based dosimetry vs. computed axial tomography tandem and ovoids (CATTO) dosimetry. Twenty-two patients with carcinoma of the uterine cervix received the brachytherapy component of their radiotherapy with a computed-tomography compatible Fletcher-Suit-Delclos device. A total of 27 implants were performed. The average maximum bladder dose (Bmax) for the implants was 85.8 cGy/hr using the CATTO system as compared to 42.6 cGy/hr using traditional dosimetry, (P < 0.005). The average maximum rectal dose (R.) using the CATTO system was 59.2 cGy/hr as compared with 46.3 cGy/hr using the traditional system (P < 0.05). The traditional methods for choosing points to determine bladder and rectal dose rates underestimated the true Bmax in all cases and the R. in most. Based on the complication rates published in the literature, it is likely that the maximum tolerance dose of both the rectum and bladder, but especially the bladder, is higher than previously thought.