tbuckley/cabot-search huggingface dataset:
A phase II clinical/translational trial of sequential axitinib/carboplatin/paclitaxel in melanoma.
Authors: A. P. Algazi, E. Cha, C. Soon, S. Ortiz-Urda, B. Cortez, L. Ziani, F. V. Coakley, A. Daud
Journal: Journal of Clinical Oncology (2011)

8528 Background: Axitinib is a potent inhibitor of VEGFR, PDGFR, and c-Kit with impressive single agent activity in advanced melanoma. We tested the hypothesis that axitinib may increase the effectiveness of carboplatin and paclitaxel in advanced melanoma, and we evaluated tumor genotype as a biomarker for response. Methods: We conducted a prospective phase II trial of this combination in previously treated patients with metastatic melanoma. Patients had an ECOG PS 0-1, and normal organ function. Axitinib 5 mg PO bid was taken on days 1 through 14 of each 21-day treatment cycle, and carboplatin at an AUC of 5 with paclitaxel at 175 mg/m2 was administered on day 1 of each treatment cycle starting with cycle 2. Pre-treatment biopsy specimens were sequenced for mutations in BRAF, NRAS, and c-KIT. FLT-PET scans are planned to assess tumor cell proliferation in a subset of patients on days 1, 14, 17, and 20 of cycle 1. Results: Axitinib with carboplatin/paclitaxel has been well tolerated with common adverse events including GI toxicity, musculoskeletal pain, fatigue, hypertension, and mild sensory neuropathy. Grade 3 adverse events have been uncommon, and grade 4 adverse events have not been observed. Five of 8 patients have had a reduction in tumor size, and, of these, 3 have had a PR by RECIST. Two patients have had PD. Of the five patients with reduction in tumor size, four were wild-type for BRAF, NRAS, and c-KIT, and one had an NRASQ61R mutation. One patient with PD and one with SD (8% tumor increase) had BRAFV600K mutations. One patient with PD had a GNAQQ209L mutation. Conclusions: Axitinib with carboplatin and paclitaxel has been well tolerated in initial testing. Treatment has been associated with a high rate of objective tumor response in melanoma, especially in those who are “triple wild-type” or NRAS mutant. Given the urgent need for effective therapies in these populations, this combination warrants further study. Patient Tumor genotype Best response (RECIST) 1 GNAQQ209L 27.0% 2 BRAFV600K 15.0% 3 BRAFV600K 8.0% 4 Wt -10.0% 5 Wt -10.5% 6 NRASQ61R -44.0% 7 Wt -44.0% 8 Wt -50.0%
Modulation of soluble c-Met, bone turnover markers, angiogenic factors, and c-Met in men with mCRPC treated with cabozantinib.
Authors: Paul G. Corn, Andreas Varkaris, Elsa M. Li Ning Tapia, John C. Araujo, Ana Aparicio, Shi-Ming Tu, Amado J. Zurita, Eleni Efstathiou, Wei Qiao, Sijin Wen, Gary E. Gallick, Christopher Logothetis
Journal: Journal of Clinical Oncology (2013)

58 Background: Cabozantinib (cabo) is a multi-TKI against c-Met and VEGFR2. Cabo elicits striking changes in bone scans (BS), reductions in soft-tissue mets, and improves bone pain in mCRPC. This unique response is unlinked from PSA and suggests that targets of Cabo reside in the bone microenvironment. To explore the underlying mechanisms of Cabo activity, we examined changes in soluble c-Met, angiogenic factors, bone specific alkaline phosphatase (BAP), and tumor specific c-Met signaling in men on Cabo. Methods: A phase II cohort of docetaxel pretreated men with mCRPC received Cabo. Response was assessed q6 wks by BS and CT scan. Blood and trans-iliac bone marrow biopsies (BMs) were collected pretreatment and at wk 6. Soluble c-Met was measured by ELISA, angiogenic factors by multiplex immunoassay, and tumor c-Met/phospho c-Met expression by IHC. Results: 21 patients with bony mets were evaluated; 38% also had soft tissue mets. 13/21 (62%) pts experienced an improvement (PRs + CRs) in BS and 2/8 (25%) achieved a PR in soft tissue mets. 12/20 (60%) pts had reductions in BAP on therapy (median reduction 48.5%). VEGFR2 levels decreased in response to therapy (p&lt;0.0001) and VEGF levels increased (p&lt;0.085). Soluble c-Met levels increased on therapy (p&lt;0.009). Pretreatment BMs containing &gt;5% tumor involvement (median 80%) were evaluable for 10 patients, 9 of whom also had a 6 wk BM. High intensity, tumor-specific expression of c-Met was detectable in 8/10 (80%) of pretreatment tumors (median involvement 60%) and increased in 4/9 (45%) pts at 6 wks (median increase 30%). Activated phospho c-Met was detectable in 9/10 (90%) of pretreatment tumors (median involvement 80%) and decreased in 5/9 (56%) pts (median reduction 30%) at 6 wks. Conclusions: The results of our study suggest that changes in soluble markers of c-Met, bone turnover, and angiogenesis are linked to Cabo activity. Analyses of BMs demonstrate high c-Met activation in pretreatment mets and suggest Cabo-mediated inhibition at 6 wks. These data support the hypothesis that c-Met contributes to “driver” signaling networks in mCRPC and suggest that biomarkers of stromal cell function should be prioritized for further study.
Diabetes mellitus in patients with multiple myeloma.
Authors: M. Mundia, A. G. Mundia, M. F. Ali, S. Ali
Journal: Journal of Clinical Oncology (2011)

e18564 Background: Dexamethasone is an effective drug in the treatment of Multiple Myeloma as a single agent and in combination with other drugs. In patients with diabetes mellitus, use of high dose dexamethasone may cause diabetes control difficult if not impossible. It was noted in our practice significant number of patients with adult onset diabetes mellitus at the time of myeloma diagnosis, leading to difficulty in use of high dose steroids. Methods: Clinical charts of 28 myeloma patients currently in our practice were compared with 28 concurrent non myeloma solid tumor patients undergoing chemotherapy to determine the incidence of adult onset diabetes mellitus. Results: Group A: There were 28 patients with Multiple Myeloma. 13 males and 15 females, their age ranging from 52 to 82 years (median 71), 14 patients were African American (AA), and 14 non African American (NAA) patients. 15 of 28 patients had adult onset diabetes mellitus at the time of myeloma diagnosis. 6 of 15 diabetic patients were AA and 9 of 15 NAA. Group B: There were 28 non myeloma solid tumor patients. 11 males and 17 females, Ages 50-86 years (median 75), There were 8 AA, and 20 NAA. 6 of 28 patients had adult onset diabetes mellitus at the time of cancer diagnosis. 2 of 6 diabetic patients were AA, and 4 of 6 diabetic patients were NAA. Conclusions: The incidence of adult onset diabetes mellitus appears to be higher in patients with multiple myeloma, and appears to be independent of age, sex, or ethnicity.
Racial differences in health care utilization in Medicare beneficiaries with metastatic prostate cancer.
Authors: Robert A. Bailey, Huai-Che Shih, Francesca Schneller, R. Scott McKenzie, Rachel Feldman
Journal: Journal of Clinical Oncology (2012)

31 Background: Racial differences in the prostate cancer (PC) incidence and outcomes have been previously reported. Patterns of PC care have been studied previously in commercially insured populations. This study evaluated racial differences in health care (HC) utilization in Medicare Beneficiaries with metastatic prostate cancer (MBMPC). Methods: MBMPCs were identified using Medicare 5% Standard Analytic Files (2002-2009) which included the Medicare fee-for-service population covered by Part A and Part B. HC costs were standardized to 2010 dollars. Patterns of care were analyzed and compared by race [White (W), Black (B), Other (O)]. Results: We identified 5,857 MBMPCs (W: 2,998, B: 748, O: 164) with a mean (SD) age 79.3 (9.4) years. Minimal differences in care were present between W and O. Compared to W, B received less outpatient care. Mean physician office visits/year: 21% fewer for all specialties (B: 10.4, W: 12.6, p&lt;0.001), 20% fewer for primary care (B: 3.5, W: 4.2, p&lt;0.001), 27% fewer for oncology (B: 2.2, W: 2.8, p&lt;0.001), and no difference in urology (B: 1.9, W: 1.9, p=0.638). There was a 50% higher number of mean hospitalizations/yr in the B group (B: 1.2, W: 0.8, p&lt;0.001). There was no difference in surgical intervention by race, however B were generally less likely to receive injection hormone therapy (HT), radiation therapy (RT), or chemotherapy (CT) prior to, concomitant to, or subsequent to the first metastatic diagnosis. Mean annual HC costs were 23% higher for B (B: $29,141, W: $23,735, p&lt;0.001), with institutional care comprising 62% of total costs for B and 52% for W. Conclusions: In MBMPC, significant differences in HC between B and W were observed. B were less likely to experience physician office visits and to receive HT, RT, or CT, and more likely to be hospitalized. Further study is warranted to identify contributing factors and potential ways to reduce these observed HC disparities including patient education and patient engagement in decision-making.
Cincinnati’s adoption of a web-based portal to promote reportable evidence-based care.
Authors: Bryan A. Loy, Jude Gallagher, Barry A. Peterson, Stanley Forston, Michael Sturgill
Journal: Journal of Clinical Oncology (2014)

121 Background: Health plans have limited ability to assess compendia and preferred pathways, as claims data lack tumor subtyping, staging, line of therapy, and performance status. Attempts by health plans to gain visibility into compendia compliance have resulted in pre-authorizations and medical record analysis, which incur administrative burdens for physicians and plans. Alternative, more efficient approaches for payers and oncologists to share clinical data on treatment decisions may promote evidence-based care. Methods: In 2011, Humana and New Century Health implemented a registry-like platform to improve administrative efficiencies and facilitate compendia and preferred pathways in participating oncology centers in the Cincinnati metropolitan area. This web-based platform replaced faxed pre-authorization forms and created the opportunity to obtain real-time authorization. In the 3 years after implementation of the platform, process metrics for breast, colon, lung cancers, and lymphoma were reported. Coverage determinations were grouped as 1) withdrawn or not approved, or 2) approved, defined as compendia-based, inclusive of pathways, off-compendia approvals, and clinical trial notifications. Results: Widespread physician adoption of the platform exceeded 99% in 2011 and remained above 95% in the following 2 years. The trends in non-approved and approved reviews remained stable. As a subset of approved-reviews, compendia-based care remained consistently above 95%, while off-compendia plus clinical trial notifications occurred at frequencies below 5%. Conclusions: Compendia compliance was high and remained stable over time. Widespread adoption of a web-based platform can ease the administrative burden and support timely enrollment of patients into clinical programs. Evolution of the platform intends to shift the information closer to the point of decision making by the treating oncologist. [Table: see text]
Patient benefit from salvage radiation for prostate cancer.
Authors: Brian Joseph Gebhardt, Andrew M. McDonald, Sejong Bae, Karan P. Singh, Rojymon Jacob, Michael C. Dobelbower, Robert Y. Kim, Eddy Shih-Hsin Yang, John B. Fiveash
Journal: Journal of Clinical Oncology (2013)

175 Background: To identify post-operative prostate cancer patients who are unlikely to achieve long-term biochemical control following salvage radiotherapy (SRT). We hypothesize that patients with node-positive disease, no nadir after radical prostatectomy (RP), or a high pre-radiotherapy (pre-RT) PSA levelwill have a low chance of benefitting from SRT. Methods: Ninety patients who received SRT following RP were retrospectively analyzed to determine factors associated with biochemical failure. Patients on continuous androgen deprivation therapy (ADT) were excluded from statistical analysis. Results: Median follow-up was 30 months (range 6-120). The overall projected 3-year bPFS was 70%. Factors significantly associated with biochemical failure on univariate analysis included Gleason score, positive seminal vesicle invasion, PSA doubling time of 6 months or less, and pre-RT PSA greater than 1.0 ng/mL. All patients with a pre-RT PSA greater than 3.0 ng/mL failed. Patients who did not reach an undetectable nadir following RP had 55% 3-year bPFS compared with 79% in those who did achieve an undetectable PSA (p=0.041). Multivariate analysis demonstrated that GS of 8 and pre-RT PSA were significant predictors. A separate analysis was performed on a subgroup of 8 patients with node-positive disease. Five patients failed at a median of 24 months (range 12-64). Of the remaining 3 patients, 2 had been maintained on long-term ADT, and 1 patient was 11 months out from treatment. Conclusions: Patients with node-positive disease are unlikely to achieve long-term biochemical control from SRT due to extra-prostatic disease spread. Although various factors may influence outcome, no other group demonstrated a very low chance of benefit. Patients with rising PSA benefit from early treatment before PSA rises above 1.0 ng/mL. [Table: see text]
The effects of age, stage, treatment, and Charlson comorbidity index (CCI) on quality of life after prostate cancer diagnosis in a single cohort.
Authors: Deanna S. Cross, Rezwan Islam, C. Daniel Mullins, Arif Hussain, Crystal Jacobson, Wendy Foth, Mark A. Ritter
Journal: Journal of Clinical Oncology (2013)

242 Background: Long term quality of life after diagnosis of prostate cancer (PC) is an important factor in determining treatment success and satisfaction. Here we investigate the quality of life in a rural cohort of individuals treated for PC within a single institution. Methods: The Expanded Prostate Cancer Index Composite (EPIC) and the Medical Outcomes Short-Form 36 (SF 36) were completed by a rural population based cohort diagnosed with prostate cancer between January of 2005 and December of 2010, enrolled in a population based biorepository. Medical records were interrogated electronically for information such as age at treatment, stage, CCI, and first course of treatment. Results: Of the 173 individuals within the cohort, we received 95 completed survey instruments. No differences in age group, stage at treatment, or treatment type between individuals who completed the survey and those who did not were observed. Median summary score for the sexual domain was 10 (min -6 max 77), median summary score for urinary domain was 85 (min 36 max 100), and median summary score for the bowel domain was 95 (min 68 max 100). Median physical health score was 80 (min 20 max 100) and median general health score was 67 (min 20 max 100). Overall satisfaction score was 75 (min 25 max 100). Scores for bowel and urinary function were not significantly associated with treatment, age, CCI, or stage at diagnosis. For the sexual domain, individuals with hormonal treatment scored worse than other treatments (ttest p=0.05). Overall physical health was associated (anova, p&lt;=0.05) with treatment, age, CCI, and stage. In a multivariate model only treatment and an interaction term with treatment and CCI were significant. Satisfaction score varied with treatment, individuals who received radiation treatment had a higher mean satisfaction score (87 vs 68 for the other groups ANOVA p=0.03). Conclusions: The treatment for prostate cancer affected an individual's quality of life in the domains of physical function, and sexual health. Treatment also affected satisfaction score regardless of age or stage at diagnosis.
The low-dose paclitaxel as first-line chemotherapy for metastatic or recurrent gastric cancer
Authors: I. Kim, J. Shin, H.-K. Kim, M. H. Lee, C. S. Kim
Journal: Journal of Clinical Oncology (2005)

4171 Background: To assess the effect and toxicity of low-dose paclitaxel in patients with metastatic or recurrent gastric cancer with measurable lesions as first-line chemotherapy. Methods: Thirty-one patients received paclitaxel 135mg/m2 (3-hour infusion) + cisplatin 60 mg/m2. Of those, one was not evaluable for efficacy analysis. Cycles were repeated every 3weeks until progression. The median age was 54 years (range 37 - 74). Sixteen patients had ECOG performance status (PS) 1 and 15 had PS 2. Objective tumor responses, duration of response, time to disease progression, overall survival, and toxicity profile are the end points evaluated in this study. Results: : A total of 122 cycles (median 3, range 1 - 12) were administered. The estimated median survival was 10.3 months, median remission duration was 5.3 months, and median progression-free survival was 3.6 months. The objective response rate was 37%: 0 CR, 11 PR, 9 SD, 10 PD. Severe toxicities were uncommon. There were 4 episodes(3.3%) of grade 3 leucopenia. Grade 3 - 4 nausea and vomiting occurred in 8.5%. Grade 3 - 4 peripheral neuropathy occurred in 4.6%. Conclusions: This low dose paclitaxel regimen (135mg/m2) showed comparable results with previously published high-dose paclitaxel regimen (175 - 250 mg/m2) used in metastatic or recurrent gastric cancer and the toxidity was minimal. A prospective randomized phase III trial is underway. No significant financial relationships to disclose.
Radiation delivery practices in nonmetastatic breast cancer at a regional cancer center in India
Authors: S. Goyal, T. Puri, G. Saini, D. N. Sharma, P. K. Julka, G. K. Rath
Journal: Journal of Clinical Oncology (2008)

11578 Background: Radiation therapy (RT) forms an integral part of treatment of breast cancer, especially in locally advanced disease. Emerging knowledge of recurrence and morbidity patterns has helped modify the treatment parameters. Methods: We retrospectively reviewed the treatment records of 213 patients treated between 1998 and 2002 to study the RT delivery practices at our department. Patients were offered surgery, RT, anthracycline- or taxane-based chemotherapy and hormone therapy depending on stage and hormone receptor status. RT was either local (chest wall or whole breast) or locoregional (local, axilla and supraclavicular region). Results: Breast cancer patients with nonmetastatic disease (n=213, 211 females, 2 males) were evaluated. Median age was 48 years (range 22–83). Stage distribution was as follows: stage I- 3 (1.4%), stage II- 73 (34.3%), stage III- 106 (49.8%) and unknown in 31 (14.6%). Surgery was performed in 206 patients- 158 (76.7%) underwent modified radical mastectomy, 41 (19.9%) had breast conservation, while the rest had suboptimal surgery. Chemotherapy was administered to 174 (81.7%) patients and hormone therapy to 121 (56.8%). RT was given to 198 patients out of which 164 (81.6%) received locoregional RT. Thirteen patients (6.5%) received internal mammary chain RT. Medial and lateral tangential treatment portals were used in 153 (77.3%) and direct chest wall field in 45 (22.7%). Photon beams were used for treatment in 157 (79.3%) and electron beams in 41 (20.7%). Median interval between surgery and commencement of RT was 144 days. At a median follow-up of 41.3 months (range 0–87.3 months) since completion of RT, 13 (6.1%) patients had experienced local recurrence, 11 (5.2%) had regional disease and 51 (23.9%) had developed distant metastases. Conclusions: Majority of patients in our country present in advanced stages of disease, and most of these ultimately receive radiotherapy to postoperative site as well as ipsilateral supraclavicular fossa and axilla. However, recent concerns over the morbidity associated with such practices and good locoregional control with adequate local surgery and axillary dissection mandate revision of these practices. No significant financial relationships to disclose.
Circulating protein biomarkers of sunitinib (SU) and interferon-α (IFN-α) efficacy in treatment (Tx)-naive patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: C. S. Harmon, R. A. Figlin, T. E. Hutson, M. D. Michaelson, S. Negrier, S. T. Kim, X. Huang, J. A. Williams, R. J. Motzer
Journal: Journal of Clinical Oncology (2011)

10525 Background: In a randomized phase 3 trial, SU demonstrated superior PFS (primary endpoint) over IFN-α as first-line mRCC therapy, with a median OS of >2 yrs (Motzer, 2009). Here, we report an investigation of potential biomarkers of SU efficacy through assessment of plasma levels of 4 soluble proteins from this trial: VEGF-A, VEGF-C, sVEGFR-3 and IL-8. Methods: 750 Tx-naïve mRCC pts were randomized 1:1 to receive oral SU 50 mg/d on a 4-week-on/2-week-off schedule or IFN-α 9 MU subcutaneously thrice weekly. Pre-dose plasma samples were collected on days 1 and 28 of cycles 1–4 and at end of Tx and analyzed via ELISA. Possible correlations between plasma protein levels and PFS or OS were assessed by univariate Cox regression analysis. Results: Baseline characteristics of biomarker-evaluated pts in the SU (n=33) and IFN-α (n=30) arms were comparable to their respective ITT populations. Compared with baseline levels, VEGF-A reversibly increased >4-fold and sVEGFR-3 reversibly decreased by >50% with SU Tx, but was unchanged with IFN-α Tx. In both Tx arms, VEGF-C changes were minimal, while IL-8 increased >50% at all time points. For each of the following regression analysis results, low soluble protein levels at baseline were associated with a lower risk of progression and/or death. In the SU arm, baseline VEGF-A, sVEGFR-3 (both P<0.005) and VEGF-C (P=0.022) correlated with PFS, while baseline VEGF-A, sVEGFR-3, and IL-8 (all P<0.0005) correlated with OS, with a trend for VEGF-C (P=0.135). In the IFN-α arm, baseline VEGF-A, IL-8 (both P<0.0001) and VEGF-C (P=0.006) correlated with PFS, while baseline VEGF-A (P=0.002), IL-8 (P<0.001) and sVEGFR-3 (P=0.048) correlated with OS, with a trend for VEGF-C (P=0.0634). Pharmacodynamic changes were not associated with PFS or OS for any plasma protein. Conclusions: Analysis of a subset of pts in a randomized phase 3 RCC study support literature evidence that high circulating VEGF-A levels are associated with poor prognosis in RCC. Results further suggest that high baseline levels of VEGF-C and IL-8 may be associated with poor prognosis in RCC, and that low plasma sVEGFR-3 levels may predict improved outcome following SU Tx.