tbuckley/cabot-search huggingface dataset:
Phase I trial of pemetrexed (P) plus docetaxel (D) in advanced malignancies
Authors: D. P. Petrylak, K. Hood, R. Xu, J. F. Gill, S. J. Nicol
Journal: Journal of Clinical Oncology (2008)

13517 Background: P and D are active in patients (pts) with advanced malignancies. This trial sought to assess the maximum tolerated dose, dose-limiting toxicities (DLTs), tumor response, and the recommended Phase II dose of a P+D combination planned for pts with advanced cancer. Methods: Pts were enrolled with noncurable cancers, ≤1 prior regimen of chemotherapy for metastatic disease, no prior RT to ≥25% of bone marrow <14 days from study entry, KPS ≥70, no symptomatic brain metastases, adequate renal and hepatic function. Cohorts of 3 pts, expanding to 6 pts with an observed DLT, were given escalating doses of P (300–500 mg/m2) and D (50–70 mg/m2) on Day 1 of a 21-day cycle. B12 and folate were given <2 weeks prior to and throughout therapy. DLTs during cycle 1 included Grade (G) 4 neutropenia >7 days or febrile neutropenia, G4 or G3 (with bleeding) thrombocytopenia, and ≥G3 nonhematologic toxicities, except nausea, vomiting or elevated G3 ALT/AST. Response for measurable disease was assessed by RECIST. Results: Eight pts enrolled with mean age of 66.1 ± 14.0 years. Four pts presented with transitional cell carcinoma of the urothelium, 3 pts with adenocarcinoma of the prostate, and 1 pt with squamous cell carcinoma of the bladder. All 8 pts received at least 1 cycle of therapy with a median of 2 cycles. Three pts enrolled at dose level 0 (P, 300; D, 60): 1 pt had G4 hypercalcaemia unrelated to therapy during post-study follow up. A fourth pt was added to dose level 0 and had G3 febrile neutropenia and G3 bacteremia. Three pts received dose level 1 (P, 400; D, 60): 1 pt had G3 dehydration while a second pt had G3 cellulitis and G3 peripheral edema. One pt received dose level 2 (P, 400; D, 70), and had G3 pyrexia, G3 cellulitis, and G4 swelling. The most common G1–4 hematologic toxicity was anemia (n=3) with 2 pts requiring blood transfusions. The most common G1–4 nonhematologic toxicities were fatigue (n=6), nausea (n=4), and constipation (n=4). The response rate was 12.5% (1/8 pts) with one pt (Stage IV adenocarcinoma of the prostate) experiencing a partial response, 4 pts with stable disease, and 3 pts with disease progression. Conclusions: Phase I of the current trial was suspended and the planned Phase II abandoned due to the limited tolerability and efficacy of this P+D regimen. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly and Company sanofi-aventis Eli Lilly and Company sanofi-aventis Eli Lilly and Company, sanofi-aventis
Fetal-maternal microchimerism: A potential novel approach for treating malignancy?
Authors: G. L. Gilmore, M. Holm, J. Lister, R. K. Shadduck
Journal: Journal of Clinical Oncology (2005)

2565 Background: Fetal-maternal microchimerism [MC] occurs during gestation or delivery, as cells traffic from the fetal circulation to the maternal circulation (and vice versa) via the placenta, and persist for decades post-partum. The reported incidence of MC is 33% in normal parous women. Methods: To explore the incidence and extent of MC among normal females and cancer patients for potential therapy, we obtained blood samples from 165 normal parous women, and 26 parous cancer patients. 31 non-parous women served as controls. The presence of male DNA was detected using two rounds of PCR with nested sets of primers specific for the Y chromosome. The sensitivity of the assay was validated at 1 male cell per 1 million female cells using DNA prepared from serial dilutions of (male) KG-1 cells in (female) K562 cells. Results: The observed frequency of MC was dependent on the amount of DNA assayed: with 1 ug DNA [∼300,000 genomes] per test, the frequency of MC was 18%. At 5 ug DNA [1.5 million genomes], this rose to 45%, and at ≥ 25 ug DNA [7.5 million genomes], 64% of normal parous women had MC. Among parous cancer patients, MC was present at 20% with 5 ug DNA, rose to 65% when ≥ 25 ug DNA or more was tested. One interesting result is that 14 out of 16 female cancer patients who had hematologic malignancies [leukemia, myeloma, CLL and NHL] were MC, while only 3 of 10 female patients with solid tumors [breast, uterine, ovarian, colon and lung cancer] were MC. 2 out the 31 normal non-parous donors were MC; this number did not increase when more DNA was assayed. The reason for the MC among non-parous subjects is unclear. We have developed a system to assess immunological tolerance in MC females, and are in the process of testing whether normal MC females are tolerant of their male offspring. Conclusions: Our results indicate the MC is much more frequent among parous women than previously reported. Provided that MC confers long-lasting tolerance of fetal tissue antigens, which we should be able to document, this suggests that son-to-mother cellular therapy may be a feasible approach for treatment of malignancy. No significant financial relationships to disclose.
A non-randomized single-center comparison of induction chemotherapy (IC) followed by chemoradiation (CRT) versus CRT for locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN)
Authors: P. M. Specenier, J. Weyler, C. Van Laer, D. Van den Weyngaert, J. Van den Brande, S. Altintas, M. T. Huizing, J. B. Vermorken
Journal: Journal of Clinical Oncology (2008)

17004 Background: Gemcitabine (GEM) is a potent radiosensitizer with activity in SCCHN. CRT is still the standard treatment for LA-SCCHN. CRT improves local control and overall survival (OS) when compared to radiotherapy (RT) alone. IC reduces the risk of distant metastases (DM) and improves OS by 5 % whith the use of cisplatin/5 fluorouracil (PF) in meta-analysis. Adding a taxane to PF confers a better outcome. Sequential treatment (ST) of IC followed by CRT is under active investigation in multiple phase III trials. Methods: We compared the outcome of two cohorts of patients (pts) with LA-SCCHN treated at our institution by CRT (12/98–09/05) or ST (03/98–09/06), respectively. Treatment: CRT: GEM 100 mg/m2 weekly + conventional RT (70 gy); ST: same CRT preceded by IC, which included DIP (docetaxel, ifosfamide, P)[16/31], TPF (docetaxel, P, F) [10/31], TPF + cetuximab [3/31] or PF [2/31]. Results: Response to IC: complete: 8, partial: 20, stable 1, progressive 1, not evaluable: 1. Median follow up (FUP) of the surviving pts: CRT: 60 months (mos), ST: 32 mos. Median time to distant metastasis (TDM): CRT: 23.5 mos, ST: not reached (NR); median OS: CRT: 20.2 mos, ST: 24.6 mos. Kaplan Meier estimate of TDM was significantly longer in the ST cohort (p= 0.013). Cox regression analysis, taking into account tumor site and nodal status, showed a hazard ratio with ST of 0.244 for TDM (p = 0.013), 0.529 for OS (p = 0.092) and 1.480 for median time to local failure (p= 0.397). Conclusions: TDM was significantly longer in the ST cohort. There was no difference in OS although there was a trend in favor of the ST cohort. These data are to be interpreted with extreme caution as this is a non-randomized single-center comparison of two rather small cohorts of pts with a different duration of FUP which were not balanced for tumor site or other prognostic factors. ST is not an accepted standard approach; the outcome of phase III trials has to be awaited. Patient Characteristics Cohort # pts Age OP HP L Other T4 N2 N3 CRT 27 57 7 17 1 2 15 13 5 ST 31 58 14 9 4 4 19 21 6 # pts = number of patients; Age = median age in years; OP = oropharynx, HP = hypopharynx, L = larynx. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen, Lilly Oncology, Merck, OXiGENE, sanofi-aventis Merck, sanofi-aventis
REOX: Effectiveness evaluation of re-exposure to oxaliplatin in patients with metastatic colorectal cancer.
Authors: Talita Gonzaga Costa, Tiago Cordeiro Felismino, Leonardo de Azevedo Boente, Celso Lopes Mello
Journal: Journal of Clinical Oncology (2016)

764 Background: Colorectal cancer has high incidence and mortality rates. Treatment of metastatic colorectal adenocarcinoma has evolved since the approval of irinotecan, oxaliplatin and monoclonal antibodies with survival surpassing 30 months in contemporary trials. Nevertheless there is paucity of effective options after failure of these protocols. Thus re-exposure to previously used drugs became a treatment strategy. We aimed to evaluate the efficacy of retreatment with oxaliplatin in mCRC and its correlation with clinicopathological features. Methods: We retrospectively analyzed 83 patients with mCRC who underwent REOX treated at a single cancer center in Brazil. REOX was defined as a second trial of an oxaliplatin containing regimen after a previous failure. Primary endpoint was time to treatment failure (TTF) after REOX. Results: Median age of our cohort was 53.5y. Female/Male: 51.8%/48.2%. Primary colon was found in 67.5% while 32.5% had primary rectal adenocarcinoma. KRAS status was wild type in 57.8% and mutated in 39.8%. Exclusive hepatic metastasis was found in 19.3%. Median follow-up after REOX was 31m. Main chemotherapy regimen was mFOLFOX6 (84.3%). Bevacizumab and Cetuximab were used in 42.2% and 6% respectively. Most patients underwent REOX in third and fourth lines, 48.2% and 25.3% respectively. Median time to treatment failure (mTTF) after REOX was 6.04m. Overall survival was 10.04m. Disease control (CR + PR + SD) was observed in 56.6%, while 42.2% had progressive disease (PD). Reasons for interruption were as follows: PD (68.7%), toxicity (19.3%) and metastasectomy (2.4%). Patients who attained disease control had better OS (14.5m) compared with patients who had PD (14.5m versus 6.24m, p &lt; 0.0001). Patients with exclusive hepatic metastasis had a trend to a better TTF compared to other metastasis sites (8.96m X 6.01m, p = 0.2). Regarding KRAS status, there was no difference in mTTF (wt 6.68m, mut 6.04m, p = 0.14). Conclusions: In the setting of pretreated mCRC patients where there are few options available, REOX remains an effective treatment, with mTTF of 6.04m in our cohort. This could be related to progression of cell clones sensitive to the drug after a time lapse since the previous exposure.
Pazopanib for treatment of metastatic renal cell carcinoma with non-clear cell histology: Single-arm, open label, multicenter, phase II study.
Authors: Ki Sun Jung, Jinhyun Cho, Kwai Han Yoo, Se Hoon Park, Jae-Lyun Lee, Se-Hoon Lee, Jae Yun Lim, Jung Hun Kang, Suee Lee, Sun Young Rha, Kyung Hee Lee, Ho Young Kim, Ho Yeong Lim
Journal: Journal of Clinical Oncology (2016)

577 Background: Targeted therapy has shown remarkable treatment efficacy on the outcomes of patients with advanced renal cell carcinoma. However, this advance for treatment outcomes with targeted agents has been limited to patents with clear cell histology. The optimal treatment strategy for metastatic non-clear cell renal cell carcinoma (nccRCC) remains uncertained. Recently, several vascular endothelial growth factor inhibitors have shown efficacies for nccRCC. Thus, we designed a single-arm, open label phase II study to determine the efficacy and toxicity of pazopanib in patients with nccRCC. Methods: Patients with metastatic nccRCC except for collecting duct or sarcomatoid type received 800mg/day of pazopanib daily until progression of the disease or intolerable toxicity was observed. The primary objectives were progression free survival (PFS) and second objectives were overall survival (OS), treatment response and safety profiles. Results: A total of 29 eligible patients were enrolled from September 2012 to August 2014. The median age of the patients was 59 years (range, 30-77 years) and 21 patients were male. The median PFS was 8.3 months (95% CI, 4.0-12.6 months) and median OS was not reached (range, 1.5-34.7 months). Among all 29 patients, five patients (17.2%) are ongoing treatment without disease progression. Disease progression was observed in 16 patients (55.2%) during follow up period. Five patients (17.2%) experienced a treatment-related toxicity of grade 3 or more during the study and they stopped treatment in the end. Eight patients (27%) expired during follow up period but, there were no treatment-related deaths. Conclusions: This prospective phase II study showed that pazopanib demonstrated promising activity and tolerable safety in patients with nccRCC (ClinicalTrials.gov NCT01538238). Clinical trial information: NCT01538238.
Understanding patient distress on day +100 of allogeneic stem cell transplant.
Authors: Leslie Jane Padrnos, Heidi Kosiorek, James L. Slack, Nandita Khera
Journal: Journal of Clinical Oncology (2016)

204 Background: Allogeneic hematopoietic cell transplantation (HCT) is a medically complicated treatment modality used for various hematologic malignancies. Patterns and predictors of distress in post- transplant setting in a contemporary cohort of patients are not well-understood. Methods: 67 patients transplanted between 12/5/12- 4/21/15 completed National Comprehensive Cancer Network Distress Thermometer as part of their long term follow up clinic evaluation on day+100 after HCT. Demographic, socioeconomic and clinical outcome data were analyzed. A score ≥ 4 was considered distressed. Results: Mean age of patients was 50.8 years (range 20-72). Most patients were married or living with their significant other (83%), half were college graduates (58%), and half were employed full time (50%). 21 patients (31%) reported a distress score ≥ 4. Distressed patients reported increased problems with treatment decisions (15% vs 2%, p&lt;0.05) and ability to have children (16% vs 0%, p&lt;0.05). Physically, distressed patients were more likely to report fatigue (85% vs 44%, p &lt;0.05), pain (60% vs 24%, p&lt;0.05) and difficulty getting around (25% vs 7% p&lt;0.05) Distressed patients were likely to report at least 1 emotional problem (N=16, 76%), and nearly a quarter reported ≥ 4 emotional problems (N=5, 24%). Specifically, sadness (25% vs 7%, p&lt;0.05) and worry (64% vs 26%, p &lt;0.01) were more common in distressed patients. Distressed patients had a longer length of hospitalization for transplant (30.8 days vs 24.9 p&lt;0.001) and more hospitalized days during the first 100 days (34.9 vs 28.7 p&lt;0.01). Conclusions: Approximately 30% of allogeneic HCT patients suffer significant distress at Day100 post-transplant. Distressed patients report problems with a variety of factors, including emotional, physical, family and practical issues that may impact function, compliance and quality of life. Higher number of hospitalized days is associated with increased distress and could be used to identify patients who may benefit from stress monitoring. Periodic screening of distress in HCT patients can help identify interventions to help improve patient reported outcomes.
Validation of a genomic classifier that predicts metastatic disease progression in men with biochemical recurrence post radical prostatectomy.
Authors: Ashley E. Ross, Mercedeh Ghadessi, Elai Davicioni, Anamaria Crisan, Christine Buerki, Nicholas Erho, Anirban Pradip Mitra, Darby J. S. Thompson, Timothy J. Triche, Felix Yi-Chung Feng, Edward M. Schaeffer
Journal: Journal of Clinical Oncology (2013)

5033 Background: Almost 50,000 men per year will present with biochemical recurrence (BCR) following local treatment for prostate cancer. These men with rising PSAs as the lone indicator of recurrence present a management dilemma due to their varied outcomes with only a proportion developing subsequent metastatic disease. Thus, there is a clear need to improve patient risk stratification in this context. Here, we evaluate Decipher, a genomic classifier (GC) in men with BCR following radical prostatectomy (RP) for its ability to predict metastasis. Methods: The 22-marker GC was validated in a prospectively designed case-cohort study of 1,010 clinically high-risk RP patients. 219 patients, including 85 who developed BCR at least 6 months post-RP were subjected to microarray analysis and GC scores were generated. Survival ROC curves, weighted Cox proportional hazards, and decision curves were used to compare the performance of the GC to Gleason score (GS), PSA doubling time (PSAdT) and time to BCR (ttBCR). Results: GC scores significantly stratified these men into those who would or would not develop metastasis after BCR (8% versus 40% of patients developed metastasis at 3 years following BCR depending on GC score category, p&lt;0.001). The AUC for GC was 0.82 (95% CI, 0.76-0.86), compared to that of GS 0.64 (0.58-0.70), PSAdT 0.69 (0.61-0.77) and ttBCR 0.52 (0.46-0.59). In decision curve analysis, the GC had the highest overall ‘net benefit’ and in multivariable modeling with clinicopathologic variables, only GC (p=0.006) and GS (p=0.046) scores were significant predictors of metastasis. Conclusions: When compared to clinicopathologic variables, the GC better predicted metastatic progression among men with BCR following RP. While confirmatory studies in additional patient populations are required, these results suggest that use of the GC can allow for better selection of men requiring additional treatment at the time of BCR.
Randomized trial of neoadjuvant chemotherapy followed by radical surgery in locally advanced squamous cell cervical carcinoma (LASCCC). Comparison of paclitaxel, cisplatin (TP), versus paclitaxel, ifosfamide, cisplatin (TIP): The SNAP-02 Italian collaborative study
Authors: R. Fossati, A. Buda, E. Rulli, F. Landoni, A. Lissoni, N. Colombo, P. Zola, D. Katsaros, R. Grassi, C. Mangioni
Journal: Journal of Clinical Oncology (2005)

5026 Background: The efficacy and tolerability of the TP regimen in the neoadjuvant treatment of LASCCC are unknown. The TIP regimen showed high efficacy but high toxicity in previous experiences and it is used as an internal control. Methods: Patients (pts) with LASCCC were randomized to receive: TP (Paclitaxel 175 mg/m2 3 h infusion + Cisplatin 75 mg/m2; n=80 pts); or TIP (Paclitaxel 175 mg/m2 3 h infusion + Cisplatin 75 mg/m2 + Ifosfamide 5 g/m2 24 h infusion with Mesna 5 g/m2 followed by Mesna 3 g/m2 12 h infusion; n=76 pts) for 3 cycles, followed by radical surgery. Pathological response to chemotherapy was classified as optimal (no residual tumor (CR) or residual disease with ≤ 3 mm stromal invasion (PR1)) or sub-optimal response (residual disease with > 3 mm stromal invasion). Primary end point of this phase II randomized trial is the rate of optimal pathological response. Results: Characteristics of the 156 eligible pts enrolled from Oct. 2000 to Jan. 2004: stage IB2 (TP=58%; TIP=62%), stage IIA (TP=13%; TIP=12%), stage IIB (TP=25%; TIP=20%), stage III (TP=4%; TIP=5%), stage IVA (TP=1%; TIP=1%), median age (TP=42 y; TIP=44 y). Response and toxicity data are available for 129 and 139 pts, respectively. The overall optimal response rate in the TP group was 30%, 95% CI=19 to 42% (12% CR, 18% PR1) and 45%, 95%CI=32 to 58% (22.5% CR, 22.5% PR1) in the TIP group. Hematologic grade 3–4 toxicities were all statistically significantly more frequent on TIP: leukopenia: (TP=7%; TIP=58%), neutropenia: (TP=26%; TIP=82%), anemia: (TP=4%; TIP=9%), thrombocytopenia: (TP=0%; TIP=17%). Conclusions: Although TP showed a satisfactory toxicity profile, its performance, in terms of optimal response rate, was below expectation since the lower 95% confidence limit of the estimate failed to reach the prespecified minimum requirement of efficacy, i.e. 22%. The TIP regimen confirmed its activity in neoadjuvant setting, but was associated with significant higher rates of grade 3 or 4 haematological toxicity than TP. No significant financial relationships to disclose.
Barriers to care faced by newly diagnosed patients with cancer.
Authors: S. K. Hendren, P. C. Raich, P. Winters, W. Thorland, S. Loader, S. Rousseau, P. Valverde, E. Whitley, K. Fiscella
Journal: Journal of Clinical Oncology (2011)

9095 Background: Cancer health disparities are due in part to barriers faced by patients of low socioeconomic status. The objective of this multi-institutional study was to characterize barriers to care faced by newly-diagnosed cancer patients. Methods: Study subjects were breast and colorectal cancer patients randomized to patient navigation in a trial of patient navigation. Multiple in-person and telephone interviews assessed barriers to care faced by patients. A standardized template and data dictionary were used. The chi-square test for independence was used to test differences between low-income (<$20K) and higher income patients. Results: 216 breast (82%) and colorectal cancer patients participated in the study. 46% had income < $20,000, and 45.8% were minority race/ethnicity (24% black, 22% Hispanic). Patients faced a median of 6.2 unique barriers, and this number surprisingly did not differ between low and higher income categories (6.3 v. 6.1 p=0.24). The most common barriers were (by decreasing frequency): (1) logistical problems with scheduling care; (2) fear; (3) transportation; (4) financial problems; (5) lack of social/practical support; (6) health insurance problems; (7) poor communication with medical personnel; (8) medical/mental health comorbidity; (9) non-English language; and (10) perceptions/beliefs about tests and treatments. Low-income patients were significantly more likely to have barriers related to adult care (32% v. 18%, p=0.02), medical/mental health comorbidity (77% v. 61%, 0.02), housing (39% v. 14%, p=0.00), and financial problems (84% v. 72%, p=0.04). Low income patients also had significantly more low health literacy, low educational attainment, minority race/ethnicity, non-English language, unmarried status, unemployment, public health insurance, and comorbidity. Conclusions: Newly-diagnosed cancer patients face a spectrum of barriers to care, and these affect both low and higher income patients. Low-income patients are particularly vulnerable to barriers related to adult care, comorbidity, housing, and financial problems. These data increase our understanding of patient factors that may interfere with cancer care, and can inform the design of interventions to address cancer health disparities.