[show abstract][hide abstract] ABSTRACT: While the benefits of exercise for managing cancer-and treatment-related side effects has been shown among various populations of cancer survivors, a relative dearth of information exists among older cancer patients. OBJECTIVES: To determine the prevalence of exercise participation during and after primary cancer treatment in older (≥65 years) and the oldest (≥80 years) cancer patients and to examine the relationships between exercise, symptoms, and self-rated health (SRH). MATERIALS AND METHODS: 408 newly diagnosed older cancer patients (mean age=73, range=65-92) scheduled to receive chemotherapy and/or radiation therapy reported symptoms and SRH prior to, during, and 6 months after treatment, and exercise participation during and following treatment. RESULTS: Forty-six percent of older and 41% of the oldest patients reported exercising during treatment. Sixty percent of older and 68% of the oldest patients reported exercising in the 6 months thereafter. Older patients who exercised during treatment reported less shortness of breath and better SRH during treatment, and better SRH following treatment. The oldest patients who exercised during treatment reported less memory loss and better SRH during treatment and less fatigue and better SRH following treatment. The oldest patients who exercised following treatment reported less fatigue, skin problems, and total symptom burden following treatment. CONCLUSION: These data suggest a willingness of older cancer patients to attempt exercise during and after treatment. Exercise during these times is associated with less severe symptoms; further clinical research examining the efficacy of formal exercise interventions to reduce symptoms and improve SRH in older cancer patients is needed.
Journal of Geriatric Oncology 04/2012; 3(2):90-97. · 1.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: Vorinostat, a histone deacetylase (HDAC) inhibitor, has shown evidence of single-agent activity in glioblastoma (GBM), and in preclinical studies, we have demonstrated significant synergistic cytotoxicity between HDAC inhibitors and proteasome inhibitors in GBM cell lines. We therefore conducted a phase II trial to evaluate the efficacy of vorinostat in combination with the proteasome inhibitor bortezomib in patients with recurrent GBM. Vorinostat was administered at a dose of 400 mg daily for 14 days of a 21-day cycle, and bortezomib was administered at a dose of 1.3 mg/m(2) intravenously on days 1, 4, 8, and 11 of the cycle. A total of 37 patients were treated, and treatment was well tolerated: grade 3, 4 nonhematologic toxicity occurred in 30% of patients and consisted mainly of fatigue (14%) and neuropathy (5%); grade 3, 4 hematologic toxicity occurred in 37% of patients and consisted of thrombocytopenia (30%), lymphopenia (4%), and neutropenia (4%). The trial was closed at the predetermined interim analysis, with 0 of 34 patients being progression-free at 6 months. One patient achieved a partial response according to the Macdonald criteria. The median time to progression for all patients was 1.5 months (range, 0.5-5.6 months), and median overall survival (OS) was 3.2 months. Patients who had received prior bevacizumab therapy had a shorter time to progression and OS, compared with those who had not. On the basis of the results of this phase II study, further evaluation of the vorinostat-bortezomib combination in GBM patients in this dose and schedule is not recommended.
[show abstract][hide abstract] ABSTRACT: The investigational arm of INT0116, a fluorouracil (FU) and leucovorin-containing chemoradiotherapy regimen, is a standard treatment for patients with resected gastric cancer with a 2-year disease-free survival rate (DFS) of 52%. Toxicity is also significant. More beneficial and safer regimens are needed.
We performed a randomized phase II study among 39 cancer centers to evaluate two paclitaxel and cisplatin-containing regimens, one with FU (PCF) and the other without (PC) in patients with resected gastric cancer. Patients received two cycles of postoperative chemotherapy followed by 45 Gy of radiation with either concurrent FU and paclitaxel or paclitaxel and cisplatin. The primary objective was to show an improvement in 2-year DFS to 67% as compared with INT 0116.
From May 2001 to February 2004 (study closure), 78 patients entered this study, and 73 were evaluable. At the planned interim analysis of 22 patients on PCF, grade 3 or higher GI toxicity was 59%. This was significantly worse than INT0116, and this arm was closed. Accrual continued on PC. The median DFS was 14.6 months for PCF and has not been reached for PC. For PC the 2-year DFS is 52% (95% CI, 36% to 68%).
Though PC appears to be safe and the median DFS favorable, the DFS failed to exceed the lower bound of 52.9% for the targeted 67% DFS at 2 years and can not be recommended as the adjuvant arm for future randomized trials.
Journal of Clinical Oncology 04/2009; 27(12):1956-62. · 18.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: Cancer patients often report cognitive impairment, manifested as problems with concentration and memory, following cancer therapy. As part of a large multicenter survey of cancer patients undergoing treatment, we investigated the frequency and severity of self-reported problems with memory and concentration over time.
A total of 595 patients undergoing treatment for solid tumors self-rated problems with memory and concentration, using an 11-point Likert scale (0 = "not present" to 10 = "as bad as you can imagine") at baseline before treatment began (T1), at their worst during treatment (T2), and at 6 months following treatment (T3). Any symptom level ≥ 7 was classified as "severe." Paired or independent t tests (as appropriate) with a Bonferroni correction were used to examine differences in symptoms over time and between patients treated with chemotherapy, radiation therapy, or both.
Concentration problems were reported by 48% of the 595 participants at T1 (5% severe), 67% at T2 (18% severe), and 58% (8% severe) at T3. Problems with memory were reported by 53% at T1 (4% severe), 67% (18% severe) at T2, and 68% (11% severe) at T3. The average frequency and severity of both symptoms in patients receiving chemotherapy, with or without radiation, increased significantly between T1 and T2 (P < .001). Both symptoms were less severe in patients receiving radiation alone at all three measurements than in either of the chemotherapy groups (all P values < .001). Symptoms at T3 were significantly higher than T1 for all groups (P < .001).
A significant proportion of patients undergoing cancer therapy self-report problems with memory and concentration. Cognitive problems get worse during treatment and are still in evidence 6 months following the conclusion of treatments.
[show abstract][hide abstract] ABSTRACT: Cancer patients vary in their preferred level of involvement in medical decision making, and responding to patients' desired level of involvement is a key element of good medical care. While the literature has clearly demonstrated heterogeneity among cancer patients' preferences, less is known about how the preferences of any given patient may change over time. This longitudinal study compared cancer patients' preferences for involvement in medical decision making from the time of diagnosis to the time of completion of therapy. Data from 729 cancer patients with mixed diagnoses were analyzed. Most patients reported a change in preferred level of involvement over time, and multivariate analysis demonstrated that patients tend to prefer a decreasing level of involvement over time (p<0.0001). Stability of patients' preferences was also associated with type of cancer, but not with other sociodemographic characteristics. The results from this study highlight the importance of reevaluating patients' preferences for involvement in medical decision making throughout the course of cancer therapy, as such preferences are likely to change.
[show abstract][hide abstract] ABSTRACT: It has been suggested that degranulating platelet alpha-granules release growth factors having a potential to modulate bone formation. The objective of this study was to evaluate the osteoconductive potential of a platelet-rich plasma (PRP) preparation.
Thirty adult male Sprague-Dawley rats were used. The PRP preparation was obtained from 10 ml of whole blood drawn from one age-matched donor rat. The preparation was processed by gradient density centrifugation and stored at -80 degrees C until use. Using aseptic techniques, the PRP preparation soak loaded onto an absorbable collagen sponge (ACS) or ACS alone was surgically implanted into contralateral critical size 6-mm calvaria osteotomies in 18 animals. Twelve animals received ACS versus sham surgery in contralateral defects. Animals were sacrificed at 4 and 8 weeks when biopsies were collected for histologic and histometric analysis.
The animals were maintained without adverse events. Bone formation was highly variable in sites receiving PRP and control treatments. Defect bone fill at 4 weeks averaged (+/-SD) 28.8+/-27.4% (PRP/ACS) versus 39.1+/-24.4% (ACS; p=0.2626) and 62.0+/-20.0% (ACS) versus 71.6+/-32.2% (sham surgery; p=0.1088), and at 8 weeks 81.0+/-12.9% (PRP/ACS) versus 64.5+/-28.1% (ACS; p=0.2626) and 75.6+/-34.1% (ACS) versus 74.1+/-24.2% (sham surgery; p=0.7353). Remnants of the ACS biomaterial were observed at both 4 and 8 weeks in sites implanted with PRP/ACS or ACS.
The results suggest that the PRP preparation has a limited potential to promote local bone formation.
Journal Of Clinical Periodontology 10/2005; 32(9):966-72. · 3.69 Impact Factor
[show abstract][hide abstract] ABSTRACT: Mantle cell lymphoma (MCL) is characterized by a t(11;14) resulting in overexpression of cyclin D1 messenger RNA. This study tested whether temsirolimus (previously known as CCI-779), an inhibitor of the mammalian target of rapamycin kinase that regulates cyclin D1 translation, could produce tumor responses in patients with MCL.
Patients with relapsed or refractory MCL were eligible to receive temsirolimus 250 mg intravenously every week as a single agent. Patients with a tumor response after six cycles were eligible to continue drug for a total of 12 cycles or two cycles after complete remission, and were then observed without maintenance.
Thirty-five patients were enrolled and were assessable for toxicity; one patient had MCL by histology but was cyclin D1 negative and was ineligible for efficacy. The median age was 70 years (range, 38 to 89 years), 91% were stage 4, and 69% had two or more extranodal sites. Patients had received a median of three prior therapies (range, one to 11), and 54% were refractory to the last treatment. The overall response rate was 38% (13 of 34 patients; 90% CI, 24% to 54%) with one complete response (3%) and 12 partial responses (35%). The median time-to-progression in all patients was 6.5 months (95% CI, 2.9 to 8.3 months), and the duration of response for the 13 responders was 6.9 months (95% CI, 5.2 to 12.4 months). Hematologic toxicities were the most common, with 71% (25 of 35 patients) having grade 3 and 11% (four of 35 patients) having grade 4 toxicities observed. Thrombocytopenia was the most frequent cause of dose reductions but was of short duration, typically resolving within 1 week.
Single-agent temsirolimus has substantial antitumor activity in relapsed MCL. This study demonstrates that agents that selectively target cellular pathways dysregulated in MCL cells can produce therapeutic benefit. Further studies of this agent in MCL and other lymphoid malignancies are warranted.
Journal of Clinical Oncology 09/2005; 23(23):5347-56. · 18.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: Platelet-rich plasma (PRP) harbors growth factors identified in bone. It has been suggested that these factors enhance osteogenesis. The objective of this study was to conduct a radiographic evaluation on local bone formation following surgical implantation of a PRP preparation using a critical-size rat calvaria defect model.
Thirty 22-week-old male Sprague-Dawley rats were used. The PRP preparation was obtained from 10 ml of whole blood drawn from one age-matched donor rat. The preparation was processed by gradient density centrifugation and stored at -80 degrees C until use. Using aseptic techniques, the PRP preparation soak-loaded onto an absorbable collagen sponge (ACS) carrier or ACS alone was surgically implanted into contralateral critical-size 6 mm rat calvaria osteotomies in 18 animals. Twelve animals received ACS alone versus sham surgery in contralateral defects. Animals were sacrificed at 4 and 8 weeks when biopsies were collected and radiographs were obtained using a standardized protocol. Three masked examiners independently evaluated the radiographic images of the defect sites. Examiner reproducibility was examined by repeat evaluation of all defect sites (r=0.6; P <0.0001).
The animals were maintained without adverse events. Defect sites in two animals receiving ACS versus sham surgery (4-week healing interval) were not evaluated due to specimen damage. Seventy-five percent of the sites (PRP/ACS or ACS) exhibited partial closure at 4 weeks; one site (ACS) exhibited full closure without significant differences between protocols (P=0.1797). Fifty percent of the sites receiving PRP/ACS exhibited full closure and 20% partial closure at 8 weeks versus 20% and 80%, respectively, for the ACS control (P=0.7532). There were no noteworthy differences between sites receiving ACS versus sham surgery at 4 or 8 weeks.
The results suggest that the PRP preparation does not have a significant effect on osteogenesis.
Journal of Periodontology 08/2005; 76(8):1287-92. · 2.40 Impact Factor