ABSTRACT
BACKGROUND: To present the early findings of a phase I clinical trial studying the use of intensity modulated radiation treatment (IMRT) to treat at risk pelvic and lower para-aortic lymph nodes in patients with high risk prostate cancer while escalating dose. Dose escalation was performed with a technique particularly aiming to limit the dose to surrounding critical structures. METHODS: A total of 12 patients were treated with an IMRT plan that delivered 45 Gy to the pelvic lymph nodes, prostate and proximal seminal vesicles. This was followed by an image guided IMRT plan that delivered 9 Gy to the prostate and seminal vesicles and then an additional 21.6 Gy delivered to the prostate for a total dose of 75.6 Gy to the prostate. Gastrointestinal (GI) and genitourinary (GU) toxicity were recorded weekly throughout treatment and in follow up (range: 20 - 49 months). RESULTS: At diagnosis, median age was 64, median PSA 15.5 (range: 5 - 103) and Gleason score ranged 7 - 9. The median dose to the bladder was 52 Gy, the median dose to the rectum was 53 Gy and the median dose to the small bowel was 26 Gy. During treatment, Grade 2 GU toxicity was noted in 3/12 (25%) patients and Grade 2 GI toxicity was noted in 2/12 patients (16%). At a median follow-up of 28 months, Grade 2 late GI toxicity was seen in 1/12 (8%) and late GU in 3/12 (25%) of patients. There were no acute or late grade 3 and 4 GU or GI toxicities. CONCLUSIONS: Our study shows the feasibility of using IMRT for pelvic and lower para-aortic nodal irradiation as the toxicities are low for the total dose that was delivered. This shows promise for reducing normal tissue doses, improving target control, and potentially allowing for additional dose escalation to the pelvic/lower para-aortic lymph nodes in our successive cohorts.
ABSTRACT
PURPOSE: Sorafenib inhibits Raf kinase and vascular endothelial growth factor (VEGF) receptor. Bevacizumab is a monoclonal antibody targeted against VEGF. We hypothesized that the complementary inhibition of VEGF signaling would have synergistic therapeutic effects. PATIENTS AND METHODS: Patients had advanced solid tumors, Eastern Cooperative Oncology Group performance status of 0 to 1, and good end-organ function. A phase I dose-escalation trial of sorafenib and bevacizumab was initiated at below-recommended single-agent doses because of possible overlapping toxicity: sorafenib 200 mg orally twice daily and bevacizumab intravenously at 5 mg/kg (dose level [DL] 1) or 10 mg/kg (DL2) every 2 weeks. Additional patients were enrolled at the maximum-tolerated dose (MTD). RESULTS: Thirty-nine patients were treated. DL1 was the MTD and administered in cohort 2 (N = 27). Dose-limiting toxicity in DL2 was grade 3 proteinuria and thrombocytopenia. Adverse events included hypertension, hand-foot syndrome, diarrhea, transaminitis, and fatigue. Partial responses (PRs) were seen in six (43%) of 13 patients with ovarian cancer (response duration range, 4 to 22+ months) and one of three patients with renal cell cancer (response duration, 14 months). PR or disease stabilization >or= 4 months (median, 6 months; range, 4 to 22+ months) was seen in 22 (59%) of 37 assessable patients. The majority (74%) required sorafenib dose reduction to 200 mg/d at a median of four cycles (range, one to 12 cycles). CONCLUSION: Combination therapy with sorafenib and bevacizumab has promising clinical activity, especially in patients with ovarian cancer. The rapidity and frequency of sorafenib dose reductions indicates that sorafenib at 200 mg twice daily with bevacizumab 5 mg/kg every 2 weeks may not be tolerable long term, and alternate sorafenib dosing schedules should be explored.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasms/drug therapy , Administration, Oral , Adult , Aged , Angiogenesis Inhibitors/administration & dosage , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Benzenesulfonates/administration & dosage , Bevacizumab , Drug Administration Schedule , Female , Humans , Male , Maximum Tolerated Dose , Middle Aged , Neoplasm Staging , Neoplasms/enzymology , Neoplasms/pathology , Niacinamide/analogs & derivatives , Ovarian Neoplasms/drug therapy , Phenylurea Compounds , Protein Kinase Inhibitors/administration & dosage , Pyridines/administration & dosage , Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors , Sorafenib , Treatment Outcome , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Vascular Endothelial Growth Factor A/blood , raf Kinases/antagonists & inhibitorsABSTRACT
PROBLEM: A number of interventions are effective in treating older children with internalizing symptoms. However, little is known about the efficacy of psychological interventions in treating younger children. This study examined the impact on internalizing symptoms of a parenting skills training program. METHODS: Forty-three parents took part in a parenting skills training program. Externalizing and internalizing behaviors were measured before and after treatment and after a 6-month period. FINDINGS: Externalizing symptoms fell after treatment. Interestingly, internalizing scores fell to an approximately equivalent degree. CONCLUSIONS: An intervention targeted towards parenting may be efficacious in the treatment of children's internalizing symptoms.
Subject(s)
Child Behavior/psychology , Education, Nonprofessional/methods , Internal-External Control , Parenting , Adult , Child, Preschool , England , Female , Follow-Up Studies , Humans , Male , Pediatric Nursing/methods , Psychiatric Nursing/methods , Treatment OutcomeABSTRACT
PURPOSE: The purpose of this cross sectional study was to evaluate the health-related quality of life of patients following maxillectomy and to compare obturation and free flap reconstruction. PATIENTS AND METHODS: At the Regional Maxillofacial Unit in Liverpool, United Kingdom, between 1992 to 1996, 39 patients underwent maxillectomy for malignant pathology. Of these patients, 28 (10 underwent obturation and 18 underwent free tissue reconstruction) completed a postoperative semi-structured interview. Eight questionnaires were used to test aspects of health-related quality of life and function. RESULTS: The main findings were the associations between the size of maxillectomy defect and the University of Washington activity (-0.53; P =.005) and recreation (-0.70; P <.001) domains, and with the physical functioning (-0.58; P =.001) and quality of life (-0.51; P =.007) domains of the European Organization for Research and Treatment of Cancer questionnaire. No statistically significant differences were seen between the obturator and free flap groups. Borderline trends were for obturator patients to be more concerned about their appearance, to have more pain and soreness in their mouths, to be more aware of their upper teeth, more self-conscious and less satisfied with their upper dentures, and less satisfied with function. CONCLUSION: Similar subjective outcomes were found for both groups, and a larger longitudinal study is needed to test these relationships more rigorously.
