Jaeckle K.A.,Mayo Clinic Florida |
Ballman K.V.,Mayo Medical School |
Giannini C.,Mayo Medical School |
Schomberg P.J.,Mayo Medical School |
And 13 more authors.
Journal of Neuro-Oncology | Year: 2010
Irinotecan has radiosensitizing effects and shows synergism with nitrosoureas. We performed a Phase II study of RT and irinotecan, followed by BCNU plus irinotecan in newly-diagnosed GBM. The MTD for patients receiving enzyme-inducing anticonvulsants (EIAC) was as follows: irinotecan 400 mg/m 2/week on Days 1, 8, 22 and 29 during RT, followed by BCNU 100 mg/m2 Day 1, and irinotecan, 400 mg/m2 on Days 1, 8, 22 and 29, every 6 weeks. The MTD for non-EIAC patients was as follows: irinotecan 125 mg/m2/week on Days 1, 8, 22 and 29 during RT, followed by BCNU 100 mg/m2 Day 1 and irinotecan 75 mg/m2 Days 1, 8, 22 and 29, every 6 weeks. Median OS was 10.8 mos. (95% CI: 7.7-14.9); OS at 12 months was 44.6% (95% CI: 33.3-59.8) and PFS 6 was 28.6% (95% CI: 18.9-43.2). Patients went off treatment due to adverse events (7%), refusal (11%), progressive disease (48%), death (9%), and other (9%); 16% completed protocol treatment. Survival was similar in patients with variant (6/7 or 7/7) and wild-type (6/6) UGT1A1*28 genotypic alleles. Grade 3-4 toxicity was more common in non-EIAC patients with variant alleles. SN-38 Cmax and AUC in EIAC patients receiving 400 mg/m2 irinotecan were 20.9 ng/ml and 212 ng/ml h, and in non-EIAC patients receiving 125 mg/m2, 15.5 ng/ml and 207 ng/ml h. SN-38 AUC varied by UGT1A1*28 status in non-EIAC patients. This regimen was not significantly active and radiosensitization was not observed. Non-EIAC patients with UGT1A1*28 variant alleles appear particularly sensitive to toxicity from irinotecan. © 2010 Springer Science+Business Media, LLC.
Kottschade L.A.,Mayo Medical School |
Suman V.J.,Mayo Medical School |
Amatruda III T.,Metro Minnesota Community Clinical Oncology Program |
McWilliams R.R.,Mayo Medical School |
And 6 more authors.
Cancer | Year: 2011
Background: There is increasing evidence that paclitaxel and carboplatin are clinically active in the treatment of metastatic melanoma (MM). ABI-007 is an albumin-bound formulation of paclitaxel that has demonstrated single-agent activity against metastatic melanoma. Methods: A parallel phase II trial was conducted in patients with unresectable stage IV melanoma who were either chemotherapy naive (CN) or previously treated (PT). The treatment regimen consisted of ABI-007 (100 mg/m2) and carboplatin area under the curve (AUC2) administered on days 1, 8, and 15 every 28 days. The primary aim of this study was objective response rate (RECIST). Results: Seventy-six patients (41 CN and 35 PT) were enrolled between November 2006 and July 2007. Three patients withdrew consent prior to starting treatment. The median number of treatment cycles was 4. There were 10 (25.6%) responses (1 complete response [CR] and 9 partial responses [PRs]) in the CN cohort (90% CI, 16.7%-42.3%) and 3 (8.8%) responses (3 PRs) in the PT cohort (90% CI, 2.5%-21.3%). Median progression-free survival was 4.5 months in the CN cohort and 4.1 months in the PT cohort. Median overall survival (OS) was 11.1 months in the CN group and 10.9 months in the PT group. Severe toxicities in both groups (Common Terminology Criteria for Adverse Effects v.3.0 ≥grade 3) included neutropenia, thrombocytopenia, neurosensory problems, fatigue, nausea, and vomiting. Conclusions: The weekly combination of ABI-007 and carboplatin appears to be moderately well tolerated, with promising clinical activity as therapy in patients who are chemotherapy naive and with modest antitumor activity in those previously treated. © 2010 American Cancer Society.
Barton D.L.,Mayo Medical School |
Burger K.,Mayo Medical School |
Novotny P.J.,Mayo Medical School |
Fitch T.R.,Mayo Clinic Arizona |
And 9 more authors.
Supportive Care in Cancer | Year: 2013
Purpose: Patients undergoing treatment for cancer often report problems with their cognitive function, which is an essential component of health-related quality of life. Pursuant to this, a two-arm randomized, placebo-controlled, double-blind, phase III clinical trial was conducted to evaluate Ginkgo biloba (EGB 761) for the prevention of chemotherapy-related cognitive dysfunction in patients with breast cancer. Methods: Previously chemotherapy naïve women about to receive adjuvant chemotherapy for breast cancer were randomized to receive 60 mg of EGB 761 or a matching placebo twice daily. The study agent was to begin before their second∈cycle of chemotherapy and to be taken throughout chemotherapy and 1 month beyond completion. The primary measure for cognitive function was the High Sensitivity Cognitive Screen (HSCS), with a secondary measure being the Trail Making Tests (TMT) A and B. Subjective assessment of cognitive function was evaluated by the cognitive subscale of the Perceived Health Scale (PHS) and the Profile of Mood States (POMS). Data were collected at baseline and at intervals throughout and after chemotherapy, up to 24 months after completion of adjuvant treatment. The primary statistical analysis included normalized area under the curve (AUC) comparisons of the HSCS, between the arms. Secondary analyses included evaluation of the other measures of cognition as well as correlational analyses between self-report and cognitive testing. Results: One hundred and sixty-six women provided evaluable data. There were no significant differences in AUC up to 12 months on the HSCS between arms at the end of chemotherapy or at any other time point after adjuvant treatment. There were also no significant differences in TMT A or B at any data point. Perceived cognitive functions, as measured by the PHS and confusion/bewilderment subscale of the POMS, were not different between arms at the end of chemotherapy. There was also little correlation between self-reported cognition and cognitive testing. No differences were observed in toxicities per Common Terminology Criteria for Adverse Events (CTCAE) assessment between Ginkgo biloba and placebo throughout the study; however, after chemotherapy, the placebo group reported worse nausea (p∈=∈.05). Conclusion: This study did not provide any support for the notion that Ginkgo biloba, at a dose of 60 mg twice a day, can help prevent cognitive changes from chemotherapy. These analyses do provide data to further support the low associations between patients' self-report of cognition and cognitive performance, based on more formal testing. © 2012 Springer-Verlag Berlin Heidelberg.
Jatoi A.,Mayo Medical School |
Thrower A.,Cedar Rapids Oncology Project CCOP |
Sloan J.A.,Mayo Medical School |
Flynn P.J.,Metro Minnesota Community Clinical Oncology Program |
And 7 more authors.
Oncologist | Year: 2010
Purpose. Rash occurs in >50% of patients prescribed epidermal growth factor receptor (EGFR) inhibitors. This study was undertaken to determine whether sunscreen prevents or mitigates these rashes. Methods. This placebo-controlled, double-blinded trial enrolled rash-free patients starting an EGFR inhibitor. Patients were randomly assigned to sunscreen with a sun protection factor of 60 applied twice a day for 28 days versus placebo. They were then monitored for rash and quality of life (Skindex-16) during the 4-week intervention and for an additional 4 weeks. Results. Fifty-four patients received sunscreen, and 56 received placebo; the arms were balanced at baseline. During the 4-week intervention, physician-reported rash occurred in 38 (78%) and 39 (80%) sunscreentreated and placebo-exposed patients, respectively (p = 1.00); no significant differences in rash rates emerged over the additional 4 weeks. There were no significant differences in rash severity, and patient-reported outcomes of rash yielded similar conclusions. Adjustment for sun intensity by geographical zone, season, and use of photosensitivity medications did not yield a significant difference in rash across study arms (p =.20). Quality of life scores declined but remained comparable between arms. Conclusions. Sunscreen, as prescribed in this trial, did not prevent or attenuate EGFR inhibitor-induced rash. © AlphaMed Press.
Roy V.,Mayo Clinic Florida |
Pockaj B.A.,Mayo Clinic Arizona |
Allred J.B.,Mayo Medical School |
Apsey H.,Mayo Clinic Arizona |
And 4 more authors.
American Journal of Clinical Oncology: Cancer Clinical Trials | Year: 2013
Objective: We conducted a multicenter phase II trial to assess the efficacy and toxicity of docetaxel and carboplatin combination as neoadjuvant therapy for stage II or III breast cancer (BC). Methods: Patients received 75 mg/m 2 of docetaxel and AUC 6 of carboplatin on day 1 followed by pegfilgrastim on day 2, every 14 days for 4 cycles, followed by definitive breast surgery. The primary endpoint was the proportion of patients achieving pathologic complete remission (pCR), defined as disappearance of all invasive and in situ tumors in the breast and axilla after chemotherapy. Results: A total of 57 women (median age, 53 y) were enrolled. Thirtyeight (67%) had ER+ , 31 (54%) PR+ , and 6 (11%) HER2 + disease; 9 had triple negative BC (TNBC). Forty-three (75%; 95% confidence interval, 62%-86%) of 57 eligible patients had clinical response (15 clinical complete response, 28 clinical partial response). Nine (16%; 90% confidence interval, 10%-28%) patients achieved pCR. Four of 9 (44%) patients with TNBC achieved pCR. Thrombocytopenia (5%) was the only grade 4 adverse event. The most common grade 3 adverse events were thrombocytopenia (19%), fatigue (12%), and anemia (9%). Conclusions: Four cycles of 2-weekly Docetaxel and Carboplatin are feasible with acceptable toxicity and a pCR rate of 16%. This regimen can be considered for neoadjuvant therapy of BC, particularly for patients not eligible for anthracycline therapy. A high pCR rate of 44% noted in a subset of patients with TNBC is encouraging and needs to be validated in large prospective trials. Copyright © 2012 by Lippincott Williams & Wilkins.
Moraska A.R.,Mayo Medical School |
Atherton P.J.,Metro Minnesota Community Clinical Oncology Program |
Szydlo D.W.,Michigan Cancer Research Consortium |
Barton D.L.,Carle Cancer Center |
And 6 more authors.
Journal of Supportive Oncology | Year: 2010
Hot flashes are a complication of androgen deprivation therapy for prostate cancer. A phase III study showed that use of low-dose gabapentin was well tolerated and moderately decreased the frequency of hot flashes due to androgen deprivation therapy when taken for 4 weeks. The current study, an open-label continuation of the randomized study, examined the efficacy and toxicity of gabapentin when taken for (an additional) 8 weeks. Patients were allowed to start, or continue, gabapentin and to titrate the dose to maximum efficacy, up to 900 mg/d. They were asked to complete a hot flash diary daily and keep weekly logs of toxicity, satisfaction with hot flash control, and quality of life. The moderate reduction in hot flash frequency and severity in the randomized phase of the study appeared to be maintained during this continuation phase. Men originally receiving the placebo or lowest dose of gabapentin (300 mg/d) had improved hot flash control relative to that at the end of the randomized phase. Minimal adverse effects were reported. These findings suggest that low-dose gabapentin is moderately efficacious for at least 12 weeks of hot flash treatment in men undergoing androgen deprivation therapy for prostate cancer and seems to be well tolerated. (NCT00028572) © 2010 Elsevier Inc.
Schild S.E.,Mayo Medical School |
Behl D.,Mayo Medical School |
Markovic S.N.,Mayo Medical School |
Brown P.D.,Mayo Medical School |
And 4 more authors.
American Journal of Clinical Oncology: Cancer Clinical Trials | Year: 2010
Objectives: This study was performed to evaluate the addition of temozolomide (TMZ) to whole brain radiotherapy (WBRT) for brain metastases from melanoma. Methods: Seven patients with brain metastases from melanoma were treated on a North Central Cancer Treatment Group (NCCTG) trial (N0274) of TMZ plus WBRT. TMZ was given orally in doses of 200 mg/m2 for 5 days every 4 weeks for up to 8 cycles. WBRT was started on the first day of TMZ and included the delivery of 3750 cGy in 15 fractions. In addition, separately analyzed was a cohort of 53 patients treated at the Mayo Clinic who received WBRT alone (39 patients) or WBRT plus TMZ (14 patients). Results: The median survival of the 7 patients treated on N0274 was 3.6 months with 2 of 7 (29%) failing in brain and 5 of 7 (71%) failing elsewhere. For the other cohort of 53 patients, the median survival was 3.8 months with WBRT alone compared 4.3 months for WBRT plus TMZ (P = 0.5). Conclusions: Patients did not appear to benefit from the addition of TMZ to WBRT for the treatment of their brain metastases. Further improvements in outcome will require research to discover more effective systemic therapy and RT techniques. © 2010 by Lippincott Williams & Wilkins.
Jatoi A.,Mayo Medical School |
Ritter H.L.,Toledo Community Hospital Oncology Program CCOP |
Dueck A.,Mayo Medical School |
Nguyen P.L.,Mayo Medical School |
And 4 more authors.
Lung Cancer | Year: 2010
Purpose: This study tested whether infliximab, a chimeric IgG1kappa monoclonal antibody that blocks tumor necrosis factor (TNF) alpha, improves/stabilizes weight loss in elderly and/or poor performance status patients with metastatic non-small cell lung cancer (NSCLC). Methods: This double-blind trial randomly assigned patients to infliximab/docetaxel (n=32) versus placebo/docetaxel (n=29). The primary endpoint was ≥10% weight gain. Results: Groups were balanced with respect to age, number of prior chemotherapy regimens, baseline weight loss, and performance status. No patient gained ≥10% baseline weight, and early evidence of the lack of efficacy prompted early trial closure. Appetite improvement was negligible in both arms. However, infliximab-/docetaxel-treated patients developed greater fatigue and worse global quality of life scores. Other outcomes, such as tumor response rate (<10% in both groups) and overall survival, were not statistically different between groups. There were no statistically significant differences in adverse events, although one death was attributed to infliximab. Genotyping for the TNF alpha -238 and -308 polymorphisms revealed no clinical significance of these genotypes, as relevant to the loss of weight or appetite. Conclusions: This trial closed early because infliximab did not prevent or palliate cancer-associated weight loss. Infliximab was associated with increased fatigue and inferior global quality of life. © 2009 Elsevier Ireland Ltd.