bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomised phase II study evaluating weekly docetaxel in combination with cisplatin and 5FU or capecitabine in metastatic oesophago-gastric cancer
Authors: Tebbutt N. , Gebski V. , Strickland A. , Gibbs D. , Walpole E. , Ganju V. , Goldstein D. , Munro S. , Harrod M. , Van Hazel G. 
Published: March 2020

4067 Background: Docetaxel (T), cisplatin (C) and 5FU (F) are active agents in oesophago-gastric cancer. A recent phase III study using TCF achieved a survival advantage but was associated with high rates of haematological toxicity (30% incidence of febrile neutropenia/neutropenic infection) as well as non-haematological side effects (Moiseyenko et al, 2005 Pr ASCO abstr 4002). Weekly docetaxel is associated with a lower incidence of haematological toxicity. This randomised phase II study aimed to test weekly docetaxel based combination chemotherapy regimens with the aim of maintaining the activity of docetaxel based combination regimens but reducing toxicity. Methods: Eligibility included; histologically confirmed, metastatic oesophageal or gastric (OG) carcinoma, measurable disease, PS0–2, adequate organ function, no prior treatment, informed consent. Pts were randomised to receive weekly (w) T 30 mg/m2 d1, 8 C 60 mg/m2 d1 F 200 mg/m2/d continuously q 3w or wT 30 mg/m2 d1, d8 and capecitabine (×)1600 mg/m2/d d1–14 q3w. The primary endpoint is confirmed response rate (RR), with each arm analysed independently. Simon’s 2 stage design was used, with 5/21 responses required in the first stage to allow continuation to 48 pts per arm. Results: 79 pts enrolled to date. Protocol specified interim analysis of efficacy after 21 pts per arm and of toxicity after 25 pts per arm ( Table ). In the first 21 pts per arm; 12 responses (11 confirmed) in wTCF arm, 6 responses (5 confirmed) in wTX arm. Trial continues accrual to target of 48 pts per arm. Complete accrual expected by April 2006. Updated data will be presented at the meeting. Conclusions: wTCF and wTX have encouraging activity and and a more favourable toxicity profile than TCF administered 3-weekly. [Table: see text] [Table: see text]
A phase II study of irinotecan, oxaliplatin, 5-fluorouracil, leucovorin (FOLFOXIRI) as a first-line chemotherapy in metastatic gastric cancer
Authors: Lee J. , Kang W. , Lee S. , Kwon J. , Kim H. , Lee H. , Lim H. , Park J. , Park Y. , Park K. 
Published: March 2020

4076 Background: Previous phase II study showed a high efficacy and safety of FOLFOXIRI (irinotecan, oxaliplatin, 5-fluorouracil, leucovorin) combination chemotherapy in metastatic colorectal cancer. This non-randomized open label phase II study evaluated the efficacy and safety of FOLFOXIRI in metastatic or recurrent gastric cancer patients. Methods: Patients with: histologically proven, bidimensionally measurable, metastatic gastric adenocarcinoma, age 18 - 70 years, with a performance status 0 - 2, no prior chemotherapy or at least 12 months after adjuvant therapy, life expectancy > 3 months, signed written informed consent were eligible. Treatment consisted of irinotecan 150 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 100 mg/m2 day and 5-fluorouracil 2000 mg/m2 as a 48-h continuous infusion starting on day 1, repeated every 2 weeks until unacceptable toxicity, patients’ refusal, or up to 12 cycles. The planned sample size was 48 and the primary endpoint was response rate. Results: From August 2004 to August 2005, 48 patients were prospectively enrolled. The median age was 54 years (24 - 69) and male:female ratio was 1.3:1. In total, 379 cycles were administered with a median of 9 cycles per patient (range, 1–12) and 45/48 patients were evaluable for treatment response. Three patients were not assessable for response due patients’ refusal for further chemotherapy following the first cycle. By per-protocol analysis, the objective response rate was 73.3 % (95% CI, 60.8–85.8) with 2 CRs and 31 PRs. Four patients (9%) had stable disease and 8 patients (18%) had progressive disease. The estimated median survival of all patients was 14.0 months (95% CI, 11.8 - 16.2 ) and the estimated median time-to-progression was 8.9 months (95% CI, 6.7–11.0). In total of 379 cycles administered, most common grade 3/4 toxicities were neutropenia (11% of all cycles) and emesis (12%). Grade 2 peripheral neuropathy occurred in 5 patients. One (2%) patient had severe tumor bleeding and 5 (10%) patients experienced grade 3 diarrhea. Conclusions: FOLFOXIRI combination chemotherapy showed a very promising preliminary anti-tumor activity and was generally well tolerated as a first-line treatment for patients with metastatic gastric cancer. No significant financial relationships to disclose.
Small bowel adenocarcinoma: A review of 491 cases
Authors: Halfdanarson T. R. , Quevedo F. , McWilliams R. R. 
Published: March 2020

4127 Background: Small bowel adenocarcinoma (SBA) is a rare tumor accounting for less than 2% of all GI tumors. The prognosis of advanced disease is poor. Benefits of adjuvant therapy following complete resection are uncertain. Methods: We retrospectively reviewed the records of 491 pts with primary SBA diagnosed at the Mayo Clinic from 1970–2005. Patients with ampullary and periampullary tumors were excluded. Results: 303 pts (62%) were male and the median age was 62 years. 280 (57%) of the tumors were located in the duodenum, 143 (29%) in the jejunum, 48 (10%) in the ileum and in 20 (9%) the location was not specified. Abdominal pain was the most common principal symptom occurring in 203 pts (43%), followed by anemia/GI bleeding in 104 pts (22%) and nausea/vomiting in 76 pts (16%). The most common histologic grading was 3, occurring in 224 pts (45%). 79 pts (16%) grade 4, 170 pts (35%) grade 2, with 7 (1.4%) grade 1. The TNM staging was as follows: 0: 3 (0.6%), I: 36 (7.3%), II: 133 (27.1%), III: 137 (27.9) and IV: 163 (33.2). In 18 pts (3.7%), data were insufficient for staging. The median survival for the entire cohort was 20.7 months, with 5 and 10 year survival 26% and 19% respectively. Increasing age (p < 0.0001), male sex (p = 0.026), advanced stage (p < 0.0001), grade 4 tumors (p = 0.005) and residual disease after surgery (p < 0.0001) were independently associated with shortened survival in a multivariate analysis. Neither adjuvant chemoradiation (n = 40) nor 5-FU based chemotherapy (n = 33) improved overall survival after complete resection, even after adjusting for age, sex, location, lymph node status and grade (RR 1.17, p = 0.45). This remained true for the subset of patients with resected duodenal tumors as well (RR 1.06, p = 0.83). The use of chemotherapy was associated with prolonged survival in patients with metastatic disease. The median survival and 1-year survival was 15.3 mos vs. 3.1 mos and 59% vs. 5.9% respectively (p < 0.0001), in this highly selected group. Conclusion: SBA is a rare tumor with a relatively poor prognosis. Complete resection of all disease offers the only chance of cure. The benefits of adjuvant therapy remain unknown, but chemotherapy in the metastatic setting may provide survival benefit. No significant financial relationships to disclose.
A combination of capecitabine and thalidomide in patients with hepatocellular carcinoma
Authors: Jeong W. , Chun H. G. , Cer D. , Sekhri V. , Kim-Schluger L. , Wolf D. 
Published: March 2020

4142 Background: Based on the single-agent efficacies observed in phase II trials (Cancer 2004;101:578–586 and Cancer 2005;103:749–755), a pilot trial with a combination of oral capecitabine and thalidomide has been conducted in patients with unresectable, recurrent or metastatic hepatocellular carcinoma (HCC) to evaluate its efficacy and toxicity. Methods: The regimen consisted of capecitabine at a dose of 750 mg/m2 po bid for 14 days every 3 weeks and thalidomide at 400 mg po bed time. Eligibility criteria included histological diagnosis of HCC, measurable disease, no prior systemic therapy, age ≥18 years, ECOG performance score (PS) of ≤2, adequate hematological, hepatic and gastrointestinal functions, no metabolic encephalopathy, and informed consent. Results: A total of 29 patients have been accrued. Two patients had never received the protocol therapy due to rapid deterioration of clinical condition after registration. Twenty-seven have been treated according to the protocol. Patient characteristics included median (range) age -60 (48–77) years; male -24; median ECOG PS -1; cirrhosis -22; hepatitis C antibody -19; hepatitis B surface antigen -4; hemochromatosis -1; extrahepatic metastasis -5. Eight patients were not evaluable for response since they received less than 2 cycles of protocol therapy. Five patients had grade 3 but asymptomatic, transient hyperbilirubinemia. Three patients had grade 1 hand-foot syndrome. Three patients had excessive somnolence which required a reduction of thalidomide dose to 200 mg. Among 19 patients evaluable for response (received ≥ 3 cycles of capecitabine), 1 patient had complete response for 5 months (Time to progression [TTP] -7 months), 4 had partial responses (TTP -2.5, 5.0, 6.0, & 7.0 months) and 4 had stable diseases for ≥ 3 months. Conclusions: This result suggests clinical efficacy of the combination of oral capecitabine and thalidomide, at given doses and schedules, with acceptable safety profile in patients with HCC (Supported by a grant from Celgene Corporation). No significant financial relationships to disclose.
Gene expression profiling identifies two distinct papillary renal cell carcinoma (RCC) subgroups of contrasting prognosis
Authors: Teh B. T. , Yang X. J. , Tan M. , Kim H. L. , Stadler W. , Vogelzang N. G. , Amato R. , Figlin R. , Belldegrun A. , Rogers C. G. 
Published: March 2020

4503 Background: Despite the moderate incidence of papillary renal cell carcinoma (PRCC), there is a disproportionately limited understanding of its underlying genetic programs. There is no effective therapy for metastatic PRCC, and patients are often excluded from kidney cancer trials. A morphological classification of PRCC into Type 1 and Type 2 tumors has been recently proposed, but its biological relevance remains uncertain. Methods: We studied the gene expression profiles of 34 cases of PRCC using Affymetrix HGU133 Plus 2.0 arrays (54,675 probe sets) using both unsupervised and supervised analysis. Comparative genomic microarray analysis (CGMA) was used to infer cytogenetic aberrations, and pathways were ranked with a curated database. Expression of selected genes was validated by immunohistochemistry in 34 samples, with 15 independent tumors. Results: We identified two highly distinct molecular PRCC subclasses with morphologic correlation. The first class, with excellent survival, corresponded to three histological subtypes: Type 1, low-grade Type 2 and mixed Type 1/low-grade Type 2 tumors. The second class, with poor survival, corresponded to high-grade Type 2 tumors (n = 11). Dysregulation of G1/S and G2/M checkpoint genes were found in Class 1 and Class 2 tumors respectively, alongside characteristic chromosomal aberrations. We identified a 7-transcript predictor that classified samples on cross-validation with 97% accuracy. Immunohistochemistry confirmed high expression of cytokeratin 7 in Class 1 tumors, and of topoisomerase IIα in Class 2 tumors. Conclusions: We report two molecular subclasses of PRCC, which are biologically and clinically distinct, which may be readily distinguished in a clinical setting. This may also have therapeutic implications. No significant financial relationships to disclose.
Phase III trial of conventional-dose chemotherapy alone or with high-dose chemotherapy for metastatic germ cell tumors (GCT) patients (PTS): A cooperative group trial by Memorial Sloan-Kettering Cancer Center, ECOG, SWOG, and CALGB
Authors: Bajorin D. F. , Nichols C. R. , Margolin K. A. , Bacik J. , Richardson P. G. , Vogelzang N. J. , Einhorn L. , Mazumdar M. , Bosl G. J. , Motzer R. J. 
Published: March 2020

4510 Background: First-line high-dose chemotherapy (HDCT) for poor-prognosis GCT PTS demonstrated improved relapse-free and overall survival compared to historical controls receiving conventional-dose regimens (JCO 1996;14:2546). Retrospective studies also showed correlations between long-term outcome and initial declines of alpha-fetoprotein (AFP) and/or human chorionic gonadotropin (HCG). This trial sought to determine: 1) if early intervention with HDCT resulted in an outcome superior to standard-dose chemotherapy and 2) whether AFP and HCG declines during cycles 1 & 2 correlated with long-term treatment outcome. Methods: PTS with untreated intermediate- or poor-risk GCT by International criteria (IGCCCG) were randomized to either 2 cycles of standard BEP (bleomycin, etoposide & cisplatin) followed by 2 cycles of HDCT (cyclophosphamide, etoposide, carboplatin) plus stem-cell rescue (BEP + HDCT) or to 4 cycles of BEP. The primary endpoint was the percent of PTS in complete response at 1 year (CR-1 yr). Based on an historical CR-1 yr of 45% for BEP, targeted accrual was 109 PTS/arm to detect a 20% improvement in PTS receiving BEP + HDCT with an alpha of 5% and 80% power. Randomization used random permuted blocks; strata were risk status (poor/intermediate) and treatment center. An independent DSMB performed one interim analysis of CR-1yr and survival in May 2000. Results: 219 PTS were randomized; 108 to BEP + HDCT and 111 to BEP alone. Final analysis demonstrated a CR-1yr of 52% for BEP + HDCT and 48% for BEP alone (P = .53 via actuarial methods). Slow marker decline PTS (AFP and/or HCG) during cycles 1 & 2 of BEP had a shorter progression-free and overall survival compared to satisfactory decline PTS (P ≤ .02) Among 70 PTS with unsatisfactory marker decline in cycles 1 & 2, the CR-1 yr was 61% for PTS receiving HDCT for cycles 3 & 4 versus 31% for those receiving 2 more cycles of BEP (P = .008). Conclusions: The routine inclusion of HDCT for intermediate- and poor-risk GCT does not improve treatment outcome. Serum marker decline during the first 2 cycles of BEP chemotherapy provides a clinically useful estimate of outcome. Research support provided by the NIH. [Table: see text]
Phase II study of volociximab (M200), an α5β1 anti-integrin antibody in refractory metastatic clear cell renal cell cancer (RCC)
Authors: Figlin R. A. , Kondagunta G. V. , Yazji S. , Motzer R. J. , Bukowski R. M. 
Published: March 2020

4535 Background: Blocking angiogenesis has been shown to be an effective strategy for controlling tumor growth in RCC. Tumor angiogenesis occurs when pro-angiogenic growth factors are released, stimulating endothelial cell proliferation and migration to form neovessels. M200 is an IgG4 chimeric monoclonal antibody that targets α5β1, thereby inducing apoptosis of proliferating endothelial cells. M200 activity is independent of growth factor stimulus, suggesting that binding of fibronectin to α5β1 occurs downstream of growth factor signalling, and is possibly a final common pathway for the development of neovasculature. Methods: This is a multicenter, open label, single cohort pilot phase II study of 40 patients (pts) with RCC. Pts received no more than 2 prior regimens. Pts received M200 10 mg/kg IV every 2 weeks until disease progression. Pts were evaluated for efficacy every 8 weeks by objective response using RECIST criteria. An independent data safety monitoring board was utilized to review safety data. Results: A total of 40 pts were enrolled. All pts were evaluable for safety and 37 pts for objective response (to date). Median age was 62.8 years. ECOG score was 0 in 27 (67.5%) and 1 in 13 (32.5%) pts. Prior nephrectomy occured in 39 (97%) pts. Other prior treatment included IL-2 in 15 (37.5%), interferon alpha in 6 (15%), IL-2 + interferon in 2 (5%) pts. Most frequent side effects were fatigue 37.5%, nausea 15% and hypertension 7.5%. Five pts died in the study, four with progressive disease (PD) and 1 with arrhythmia (unrelated to M200). SD was observed in 32/37 (87%) of pts. No changes in hematological, renal and hepatic parameters were noted. Median time to progression was 113+ days. The average peak and trough concentrations of circulating M200 following 6 weeks of treatment were 390 μg/mL and 140 μg/mL, respectively. There were no detectable immune responses to M200. Conclusions: M200 is well tolerated at 10 mg/kg Q2W. Stable disease is noted in 87% of pts. Follow-up continues. A higher dose level is being evaluated. [Table: see text]
Prospective trial of ifosfamide, paclitaxel, and cisplatin (ITP) in patients with advanced non-transitional cell (non-TCC) carcinomas of the urothelial tract
Authors: Galsky M. D. , Iasonos A. , Mironov S. , Scattergood J. , Donat S. M. , Bochner B. H. , Herr H. W. , Russo P. , Boyle M. G. , Bajorin D. F. 
Published: March 2020

4542 Background: Non-TCC’s account for 5–10% of urothelial tract tumors and are each characterized by unique demographics, risk factors, and patterns of spread. A unifying feature of these malignancies is their aggressive course and poor outcomes with standard chemotherapeutic regimens. Given the rarity of these tumors, no prospective data are available to guide management. Methods: Patients with unresectable/metastatic adenocarcinoma, squamous cell, small cell, sarcomatoid, and poorly differentiated carcinomas of the urothelial tract were eligible. Treatment consisted of: Paclitaxel 200 mg/m2 IV on day 1, cisplatin 70 mg/m2 IV on day 1, ifosfamide 1500 mg/m2 IV on days 1–3 + mesna. GCSF was administered with each cycle. Treatment was recycled every 3 weeks for a maximum of 6 cycles. The primary endpoint was the response rate. Results: Twenty patients (pts) were enrolled with the following histologic types: adenocarcinoma 11/20, squamous cell carcinoma 8/20, small cell carcinoma 1/20. Pts received a median of 4 cycles (range, 1–6). The grade 3–4 toxicities included neutropenia (6/20), anemia (9/20), thrombocytopenia (4/20), confusion (1/20), seizure (1/20), neuropathy (1/20), renal insufficiency (2/20), fatigue (2/20), and hyponatremia (1/20). Thirteen of the 20 pts have died. The median survival for pts with adenocarcinoma is 24 months (95% CI 9.6–32.4) and with squamous cell carcinoma is 8.4 months (95% CI 5.3-NR). Five pts achieved durable disease-free survival (1+, 2+, 4+, 6+, and 8+ years) after ITP ± surgical consolidation. Conclusions: ITP is an active regimen in pts with advanced non-TCC’s of the urothelial tract. To our knowledge, this is the first prospective study of a chemotherapeutic regimen in this patient population. [Table: see text] [Table: see text]
Clinical outcome of patients managed for late relapse of germ cell tumor
Authors: Sharp D. S. , Carver B. S. , Eggener S. E. , Kondagunta G. V. , Motzer R. J. , Bosl G. J. , Sheinfeld J. 
Published: March 2020

4550 Background: The significance of late relapse (LR) of germ cell tumor (GCT) and its association with poor survival is becoming increasingly recognized. Methods: Between 1990 and 2004, 75 patients (pts) were managed for LR of GCT at MSKCC. Using our prospective databases and following IRB approval, clinical and pathologic parameters were reviewed. Estimates of cancer-specific survival were generated using the Kaplan-Meier method and Cox-proportional hazards model was used to assess for predictors of outcome. Results: Clinical stage (CS) at initial presentation was I in 15 (21%), II in 32 (44%), and III in 26 (36%) of pts. Management prior to LR included surveillance in 10 (13%) pts, RPLND only in 8 (11%) pts, chemotherapy only in 19 (25%) pts, and both chemotherapy (induction or adjuvant) and RPLND in 38 (51%) pts. The median time to LR was 6.8 (2.1–37.7) years. Overall, 56/75 (75%) of pts had LR in the retroperitoneum (RP), including 25 of 27 (93%) initially managed without RPLND prior to LR. At LR, 45/75 (60%) of pts were symptomatic and 46/75 (61%) pts had elevated serum tumor markers (STM) (78% AFP and 39% βHCG). Overall 5 year cancer-specific survival (CSS) was 59% (95% CI 47%–72%). Pts who underwent complete resection (with or without salvage chemotherapy) at time of LR (n = 44) had a 5 year CSS of 77% (95% CI 62%–92%). In contrast, 5 year CSS for patients treated without complete surgical resection (n = 31) was 39% (95% CI 21%–57%) (p = 0.0001). The pathology of 69 pts at LR revealed viable GCT in 39 (57%), only teratoma in 13 (19%), malignant transformation in 14 (20%), and fibrosis in 3 (4%). A multivariable analysis of pretreatment parameters showed that at time of LR, a solitary site of metastasis (HR 2.6, 95% CI 1.1–6.2, p = 0.03) and no prior chemotherapy (HR 4.2, 95% CI 1.2–14.2, p = 0.02) were predictive of improved cancer-specific survival. Elevated STM and presence of symptoms did not impact survival independently in this model. Conclusions: Although LR of GCT is associated with poor survival, pts who are chemotherapy naïve and have a solitary metastatic site at LR experience improved survival. The data suggest that meticulous control of the RP is critical to prevent LR in the RP. Survival is greatly improved if complete surgical excision of disease at LR is attained, highlighting the critical role for surgery in these patients. No significant financial relationships to disclose.
Metabolic syndrome predicts for shorter response to hormonal therapy in prostate cancer
Authors: Flanagan J. R. , Carney-Doebbeling C. , Jones L. , Sweeney C. 
Published: March 2020

4554 Background: Metabolic syndrome (MS) includes obesity, insulin resistance, dyslipidemia and hypertension. Recent studies have linked the individual components of MS to an increased risk for prostate cancer (PC) and worse PC outcomes. Methods: A retrospective chart review was performed on 100 consecutive patients treated for prostate cancer at a Veteran’s Administration oncology clinic between 1998–2005. MS was diagnosed according to Adult Treatment Panel III criteria, and was present with ≥3 of 5 components: hypertension (SBP ≥140 mmHg and/or DBP ≥90 mmHg on 2 outpatient visits; obesity (BMI ≥30); hypertriglyceridemia (>150 mg/dL on 2 fasting laboratories); LDL 110 mg/dL (2 outpatient am values while not on steroids). PC variables included baseline PSA at time of PC diagnosis, PSA at initiation of hormonal therapy (HT), presence of documented metastasis at time of HT, and primary PC treatment. We examined time to PSA progression (TTP) and median overall survival (OS) for PC among patients with and without MS using Kaplan-Meier curves and Cox proportional hazard models. Results: 83 patients treated with HT for PC were identified, and 41 (49%) met criteria for MS. Median age in both groups was 68. Median TTP was 16 months with MS vs. 46 months without MS (p = 0.001). In those patients with documented metastasis (DM) at time of HT, median TTP was 11 months with MS vs. 32 months without MS (p = 0.006). OS from time of HT was 40 months with MS, and median survival time for no MS was not reached. In multivariate regression analyses, the hazard ratio (HR) for increased TTP with MS was 3.49 (95% CI 1.86–6.54). HR for TTP with documented metastasis was 5.3 (95% CI 2.65–12.8). Conclusions: This retrospective analysis suggests patients with MS treated with HT for PC have significantly shorter time to PSA progression and worse overall survival. This analysis supports the need for a prospective evaluation of MS as a risk factor for early development of HRPC. [Table: see text] No significant financial relationships to disclose.