bluuebunny/crossref_metadata_2025_split huggingface dataset:
NCCTG phase II trial of bevacizumab, gemcitabine, oxaliplatin in patients with metastatic pancreatic adenocarcinoma
Authors: Kim G. P. , Oberg A. , Kabat B. , Sing A. , Hedrick E. , Campbell D. , Alberts S. 
Published: March 2020

4113 Background: The combination of gemcitabine and oxaliplatin (GemOx) is a highly active regimen in pancreatic cancer. A recent study with the biologic agent, bevacizumab, and gemcitabine has also demonstrated significant activity. A phase II study is ongoing to evaluate whether combining an active cytotoxic doublet with an effective targeted agent improves 6-month survival and is tolerable in previously untreated patients (pts) with metastatic pancreas cancer. Methods: Treatment consists of gemcitabine 1000 mg/m2 IV over 100 minutes and bevacizumab 10 mg/kg IV given on day 1 and 15; oxaliplatin 100 mg/m2 IV is given on day 2 and 16. A treatment cycle consists of 28 days. Eligibility includes: no prior chemotherapy, ECOG PS 0–2, bili < 2× UNL, AST < 5× UNL. Pts with stable full-dose anticoagulation are eligible. Bevacizumab specific exclusions include no recent stroke, heart attack, embolus, tumor invasion or significant proteinuria. CT scans are obtained every 2 cycles. Treatment continues until disease progression, toxicity or patient refusal. Results: Sixty-three patients of a planned 75 were enrolled from 7/05 to 1/06; 2 cycles of toxicity data are available on 31 of the first 32 consecutive pts. The overall grade 3+ toxicity rate is 52% (16/31); more specifically, the grade 3 toxicities were 42% (13/31) and the grade 4 rate is 10% (3/31). Grade 3 adverse events are nausea (4), vomiting (4), alk phos (3), dehydration (3), thrombosis (2), leukopenia (2), neutropenia (4), abdominal pain (2), hypokalemia (4), and one each of the following: anorexia, low consciousness, pneumonia, rectal pain, diarrhea, and proctitis. There was one patient death due to cerebral ischemia (grade 5: 1/31 or 3%). Conclusions: Early assessment of toxicity in this trial reveals a reasonably tolerable regimen. Addition of bevacizumab to GemOx appears to have grade 3/4 toxicity rates similar to historical observations (ECOG 6201). Toxicity data for all patients, after at least 2 cycles of treatment, will be presented. [Table: see text]
Gemcitabine-based polychemotherapy for advanced pancreatic cancer (APC): Is it ready for prime time? A pooled analysis of 3,682 patients (pts) enrolled in 12 phase III trials
Authors: Milella M. , Carlini P. , Gelibter A. , Ruggeri E. , Ceribelli A. , Pino M. , Terzoli E. , Cognetti F. , Giannarelli D. , Bria E. 
Published: March 2020

4118 Background: Since the introduction of gemcitabine (G), attempts have been made to develop G-based combination regimens to improve the dismal outcome of APC pts. Results of randomized trials, however, have been conflicting and single-agent G presently remains the standard of care for such pts. Methods: All prospective phase III trials comparing single-agent G with G-based polychemotherapy regimens (poly-G) were considered eligible. A pooled analysis was performed and event-based relative risk ratios (RR) with 95% CI were derived through both a fixed- and a random-effect model approach, exploring OS as the primary outcome and PFS and ORR as secondary outcomes. Heterogeneity between different trials was also taken into account. Results: Twelve trials involving 3682 pts were identified. The analysis was conducted considering three different subgroups: 1) overall population (3682 patients, 12 trials), 2) platinum-containing poly-G (PG) vs G (768 pts, 5 trials), and 3) fluoropyrimidine-containing poly-G (FG) vs G (1640 pts, 4 trials). As shown in the table, no significant differences in the primary outcome (OS) were observed in any of the three groups analyzed. Conversely, a significant advantage for poly-G was evident with regard to both PFS and ORR in the overall population as well as in the PG vs G subgroup, although with some heterogeneity. A heterogeneous non-significant trend towards a better PFS and ORR outcome was also observed in the FG vs G subgroup. Conclusions: Single-agent G remains the treatment of choice in APC pts. However, the addition of platinum compounds to G appears to significantly improve PFS and ORR, possibly justifying the use of platinum-based poly-G in younger and fit patients. [Table: see text] No significant financial relationships to disclose.
A phase II study of triapine in combination with gemcitabine (G) in patients (pts) with unresectable or metastatic pancreatic cancer (PC)
Authors: Greeno E. , Kindler H. L. , Peeters M. , Trowbridge R. C. , Chong G. , Valle J. W. , Johnson B. , Allain E. L. , Burris H. A. 
Published: March 2020

4123 Background: Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone [T]) is a small molecule that inhibits ribonucleotide reductase at a site distinct from G. In tumor cell lines, pre-exposure to T enhances G uptake and DNA incorporation, and yields synergistic cytotoxicity. A phase I trial of T + G showed that the combination was well-tolerated and produced T serum concentrations sufficient to modulate G activity in vitro (Ca Chemother Pharmacol, 2004). Methods: We conducted a phase II trial of T + G in advanced PC pts at 7 centers. Eligible pts were untreated, had measurable disease and ECOG PS 0–2. T was given by 4-hr infusion followed by G 1000 mg/m2 on days 1, 8, and 15 of a 4-week schedule. Since preclinical studies showed longer exposure of T maximized synergy between the agents, the protocol was amended to administer T over 24 hrs continuously (CI) prior to G. Pts were assessed for response q 2 cycles and retreated to progression or toxicity. Results: Sixty pts (median age 62, range 37–88) were treated with T by 4-hr infusion (median 4 cycles, range 1–18). Pt characteristics included M:F 39/21; PS 0/1/2 = 25 (42%)/34 (57%)/1 (2%); metastatic/locally advanced 72/28%. Eight (15%) patients achieved PR; and 32 (60%) had stable disease. Median survival was 8 mos; 13% are alive at 1 yr. The next 6 pts (median age 54, range 50–69, M/F: 3/3) received T at a fixed dose of 400mg CI + G. Two pts were evaluable for response; 1 pt had PD, 1 pt is on treatment after 14 cycles. Due to excessive myelosuppression the dose of T CI was reduced to 105 mg/m2. Of 7 pts (median age 60, range 34–73) treated, 2 had PD, 1 was unevaluable, and 4 remain on tx. T toxicity included hypotension, hypoxia, rash and dyspnea in < 10% of pts. In the 2 CI groups (N=13), the only toxicity attributed to T was excessive myelosuppression, requiring G dose reduction in all pts. Survival data on CI pts pending. Conclusions: T + G shows activity in PC. As predicted by preclinical studies, prolonged exposure (CI) enhances biological effect of T + G evidenced by increased myelosuppression without additional toxicities. Further studies are warranted to define the optimal dose of T CI with G. [Table: see text]
Image-guided intensity modulated radiation therapy (IG-IMRT) affords increased survival for biliary tract tumors: Results from preliminary analysis
Authors: Starling G. , Fuller C. D. , Thomas C. R. , Fuss M. 
Published: March 2020

4131 Background: The purpose of this study is to determine the effect of image-guided radiotherapy on survival in adenocarcinoma of the biliary tract. Methods: Between 1995 and 2005, 43 pts with primary biliary tract (gallbladder or bile duct) neoplasms were treated with radiotherapy. 26 of the pts were female and 17 were male. Their average age at registration was 64, and ranged from 25 to 86. Twenty-five pts (58%) were Hispanic, while 18 (42%) were white. 31 pts (72%) underwent surgical treatment, most having cholecystecomy (50%). 29 pts (67%) had chemotherapy: 21 (72%) were given fluorouracil-based drugs, 2 (7%) received gemcitabine, and 6 (21%) received other agents. 23 pts (53%) received conventional radiation treatment using AP/PA, AP/PA with opposing lateral, or AP with opposing lateral fields. 20 pts (47%) received IG-IMRT using Nomos Peacock and daily ultrasound image guidance (BAT, Nomos, Cranberry, PA). For daily ultrasound-based image-guidance, sagittal and axial ultrasound images were acquired, and used to align pt anatomy through superimposition of CT derived organ and vascular guidance structures. Pts were treated using a boost technique to a reduced volume at gross disease after an initial dose to gross tumor and clinically evident microscopic disease. Results: Median dose to target was 54 Gy, with median conventional and IG-IMRT total doses of 48.6 and 60 Gy respectively (p=0.05). Treatment was well tolerated, with only two patients reporting RTOG grade 3 toxicity. All other patients exhibited Grade ≤2, with 23/43 reporting Grade ≤1 The median survival time from the date of registration for all patients was 8.7 months; conventional RT pts had a median survival of 6.1 months, while the IG-IMRT cohort had a median survival of 11.4 months (p = .02). Conclusions: Ultrasound-based image-guided IMRT is a feasible mechanism of delivering moderate dose escalation in conjunction with tighter safety margins, resulting in acceptable acute toxicities. Early survival data with this novel technique are encouraging and demonstrate a notable survival differential using image guided radiotherapy as component of multi-modaility regimens. No significant financial relationships to disclose.
A prospective multicenter phase II trial of capecitabine plus oxaliplatin (CapOx) in advanced biliary system adenocarcinomas: The final results
Authors: Nehls O. , Oettle H. , Hartmann J. , Hofheinz R. , Hass H. , Hochhaus A. , Stieler J. , Koppenhöfer U. , Gregor M. , Klump B. 
Published: March 2020

4136 Background: To investigate the safety and efficacy of capecitabine and oxaliplatin combination therapy (CapOx) in unresectable or metastatic adenocarcinomas of the biliary system. Methods: 65 patients (pts) (27 male, and 38 female) were enrolled (median age, 61 yrs). Major eligibility criteria: histologically proven, measurable disease, age ≤ 75 yrs, ECOG PS 0–2. A total number of 364 cycles (median, 5; range, 1–16) of oxaliplatin (130 mg/m2, d1) plus capecitabine (2 g/m2, d 1–14) were administered 3 weekly for gallbladder carcinoma (GBC) (27 pts), extrahepatic (20 pts), and intrahepatic (18 pts) cholangiocarcinoma (CCC). Response rates were assessed according to WHO criteria. Clinical outcome was determined separately for pts with either GBC/extrahepatic CCC or intrahepatic CCC (mass-forming type). Results: Grade 4 toxicities (WHO): diarrhea in 1 pt (1% of cycles), thrombocytopenia in 1 pt (1%), leukocytopenia in 1 pt (1%), and fever in 2 pts (1%); grade 3 toxicities: nausea/vomiting in 1 pt (1%), diarrhea in 2 pts (1%), thrombocytopenia in 3 pts (2%), and fever in 1 pt (1%). Grade 3/4 peripheral sensory neuropathy (Lévis scale) was found in 13 pts (14% of cycles). Two pts were excluded from study because of oxaliplatin-related allergic reactions. One patient died due to sepsis and another due to cerebral insult during the first treatment cycle. The overall disease control rate in 47 pts with GBC or extrahepatic CCC was 72% (complete response (CR), n = 2 (4%); partial response (PR), n = 11 (23%); stable disease (NC), n = 21 (45%)), whereas progressive disease (PD) was found in 13 pts (28%). In 18 pts with intrahepatic mass-forming CCC, no CR or PR was observed, 5 pts (28%) had SD, and 13 pts (72%) experienced PD. Conclusions: The CapOx protocol is well tolerated and remarkably active for advanced GBC as well as extrahepatic CCC with a disease-control rate of 72%. However, activity appears to be limited in the subset of pts with intrahepatic mass-forming type tumors. Survival data will be presented at the meeting. No significant financial relationships to disclose.
A proposed staging system for diffuse malignant peritoneal mesothelioma patients undergoing cytoreductive surgery and perioperative intraperitoneal chemotherapy
Authors: Sugarbaker P. H. , Yan T. , Yoo D. , Brun E. , Cerruto C. , Chang D. 
Published: March 2020

4150 Background: There is no staging system available for diffuse malignant peritoneal mesothelioma (DMPM). This study evaluated seven clinical, seven radiological and twelve histopathologic prognostic parameters for survival of patients with DMPM. Methods: Between September 1989 and September 2005, sixty-two DMPM patients who were treated in a uniform fashion utilizing cytoreductive surgery combined with heated intraoperative intraperitoneal chemotherapy, with cisplatin and doxorubicin, followed by early postoperative intraperitoneal paclitaxel from postoperative day 1 to day 5 were included in this study. All prognostic parameters were analyzed in univariate and multivariate analyses using overall survival as the endpoint. The clinical and radiological data were obtained prospectively. A review of the histopathological features of DMPM was performed by two experienced pathologists, who individually evaluated each case. The mean number of specimens taken from separate anatomic sites was 11 ± 4 per patient. The mean number of slides studied was 20 ± 8 per patient. Results: The median follow-up was 37 months (range 8 to 143 months). The overall survival was 79 months (range 1 to 143 months) and 5-year survival was 50%. The following 14 prognostic variables were significant for survival in the univariate analysis: gender (p = 0.045), peritoneal cancer index (p = 0.038), completeness of cytoreduction score (p = 0.010), interpretive CT findings of the small bowel (p = 0.001), histologic type (p < 0.001), nuclear size (p < 0.001), nuclear/cytoplasmic ratio (p < 0.001), mitotic count (p < 0.001), atypical mitosis (p < 0.001), chromatin pattern (p < 0.001), cellular necrosis (p < 0.001), perineural invasion (p = 0.037), stroma pattern (p < 0.001) and depth of invasion (p = 0.014). In the multivariate analysis, the only factor that was independently associated with an improved survival was nuclear size. The 3-year survival rates with nuclear size of 10–20 μm, 21–30 μm, 31–40 μm and > 40 μm were 100%, 87%, 27% and 0%, respectively. Conclusions: Nuclear size was the dominant factor determining overall survival in patients with DMPM. A histopathological staging system based on measurement of the nuclear size was proposed. No significant financial relationships to disclose.
Treatment of HIV positive anal cancer patients with chemoradiation
Authors: Hwang J. M. , Rao A. , Shieh E. , Yao J. , Tome M. 
Published: March 2020

4154 Background: Tolerance and outcomes of HIV+ anal cancer patients are questioned, especially since the emergence of High Active Anti-Retroviral Therapy (HAART) in the mid-1990s. Our experience in treating these patients before and during the HAART era is reported. Methods: From 1987–2003, 19 HIV+ invasive anal cancer patients were treated with: 30–60 Gy pelvic RT (2 Gy/d) + Mitomycin C (10 mg/m2 bolus on d1) + 5-FU (1000 mg/m2/d, continuous infusion d1–4 and 28–31). Results: Mean CD-4 count at cancer diagnosis was 311, with 9 on HAART. Mean CD-4 count for HAART was 383 and 247 for non-HAART. Stage distribution: 1 T1, 9 T2, 9 T3, 18 N0, 1 N3. Mean f/u was 40 months. 79% had complete response after chemoRT. 4 had locally persistent disease. There was 1 loco-regional recurrence and 2 distant metastases. 79% of the cohort is colostomy-free. Median OS has not been reached. OS at 2 and 3 years were: 88%and 79%, with 10 Alive and NED, 1 Alive with disease, 3 Dead of disease, 5 Dead from intercurrent disease (all secondary to AIDS). 1.5 year DFS was 74%. Break and CD-4 count < 200 had a statistically significant negative impact on DFS, but not OS. HAART did not affect either factor. 11 had RT break for median of 17 days. There was no Grade 4 skin toxicity. All completed the 2nd 5-FU cycle: 7 had delay (median 7 days) and 3 had dose decrease. There were 6 hospitalizations: 5 neutropenic fevers and 1 perineal abscess rupture. WBC Toxicity: 6-Grade 3 and 2-Grade 4. Platelet Toxicity: 2-Grade 3. Heme toxicity was not affected by HAART or CD4 count < 200. There were no treatment related deaths. Conclusion: HIV+ anal cancer patients have reasonable tolerance and outcomes with chemoRT. CD-4 count < 200 and break were negative prognostic factors for DFS. Our 79% colostomy free survival is similar to RTOG 9208, where suboptimal control was attributed to mandatory RT break. Factors influencing break include heme and skin toxicity. To improve the therapeutic ratio, substitution of Mitomycin-C with Cisplatin, IMRT, and Ethyol are being explored. No significant financial relationships to disclose.
Bevacizumab with or without erlotinib in metastatic renal cell carcinoma (RCC)
Authors: Bukowski R. M. , Kabbinavar F. , Figlin R. A. , Flaherty K. , Srinivas S. , Vaishampayan U. , Drabkin H. , Dutcher J. , Scappaticci F. , McDermott D. 
Published: March 2020

4523 Background: Bevacizumab (B) has clinical efficacy in metastatic RCC following cytokine treatment. A single-arm Phase II trial suggested potential clinical benefit of adding erlotinib (E) to B. To further assess this combination in RCC, we conducted a multicenter, randomized, double-blind Phase 2 trial comparing B+E vs B + placebo. Methods: Eligibility criteria included: previously untreated metastatic RCC with >50% clear cell histology; previous nephrectomy; ECOG PS 0 or 1; measurable disease; serum Ca++ ≤ 10 mg/dL; LDH ≤ 1.5 ULN; Hgb ≥ 9 g/dL; and standard exclusion criteria for B. All pts received B 10 mg/kg IV q 2 wk with either E 150 mg po daily or placebo until disease progression or unacceptable toxicity. Tumors were assessed using RECIST every 8 wks. A landmark analysis was performed 9 mo after accrual of the last pt. Objective response rate (ORR) and progression-free survival (PFS) were co-primary endpoints. Secondary endpoints included response duration, overall survival, and safety. Results: 104 pts (53 B, 51 B+E) were enrolled at 20 sites from Mar 2004–Oct 2004. 65 pts have discontinued therapy. 55 have progressed (PFS HR = 0.86, CI 0.5, 1.49). Median follow-up was 9.8 mo. Median survival duration was not reached. Only 1 treatment-related death due to GI perforation occurred (on B+E). Updated safety and survival data will be presented. Conclusions: B+E and B were well tolerated. Adding E does not appear to improve efficacy from B. PFS of 8.5 months with B compares favorably with the historical PFS of ∼ 4.7 mo with interferon alpha (IFN). Results of phase III trials comparing IFN ± B are pending. [Table: see text] [Table: see text]
The von Hippel-Lindau gene mutation is associated with the good-prognosis profiling subtype of clear cell renal cell carcinoma
Authors: Tan M. , Teh B. 
Published: March 2020

4532 Background: The prevalence of von Hippel-Lindau (VHL) mutations in clear cell renal cell carcinoma (ccRCC) is about 30–50%. The association between VHL mutation and patient prognosis remains controversial, despite extensive in vitro research on its role in hypoxia response. We have previously reported a robust prognostic classification of ccRCC using gene expression profiling. In view of reports of activity of anti-angiogenesis agents, we studied the association of VHL mutation with tumor profiling subtypes, survival and other clinical parameters. Methods: All exons of the VHL gene in 88 ccRCC samples were sequenced. Expression profiling using oligonucleotide arrays (54,675 probe sets) was also performed, and the samples classified using hierarchical clustering. For identification of VHL mutation specific signatures, nearest shrunken centroids with internal validation was used with a 10% misclassification cutoff. Results: 35% of the samples had VHL mutations. Mutation status was not significantly associated with survival on univariate analysis (p = 0.54). Hierarchical clustering yielded two ccRCC subtypes with divergent clinical outcomes (HR = 4.13, p < 0.001). VHL mutations were significantly associated with the good-prognosis profiling subtype of ccRCC tumors (OR 3.3, p = 0.04), but no effect modification between VHL mutation and the prognostic subtypes was found (p=0.31). No standard clinical parameter was associated with VHL mutation. No significant association between VHL mutation and downstream hypoxia response gene expression, including VEGF (p = 0.14), PDGF (p = 0.5), TGF-A (p = 0.24) and GLUT1 (p = 0.45) was found. Conclusion: While VHL mutation is associated with a biologically distinct good-prognosis profiling tumor subtype, its lack of prognostic value on univariate analysis suggests an expanded study to evaluate effect modification. The absence of a specific gene classifier for VHL mutation and the lack of association between VHL gene mutation and known hypoxia response genes suggest that VHL mutations result in heterogenous tissue phenotypes. These results support molecular subtyping of ccRCC in laboratory and clinical studies; in particular, this may be critical for trials involving anti-angiogenesis agents. No significant financial relationships to disclose.
Perioperative chemotherapy treatment patterns in stage III transitional cell carcinoma (TCC) (1998–2003): A report from the National Cancer Data Base (NCDB)
Authors: David K. A. , Nanus D. M. , Milowsky M. I. , Ritchey J. , Stewart A. , Carroll P. R. 
Published: March 2020

4540 Background: Studies have demonstrated benefits of perioperative chemotherapy in locally advanced TCC. We reviewed chemotherapy treatment patterns in patients with stage III TCC of the bladder and upper urinary tract (UUT) between 1998–2003 to investigate the use of perioperative chemotherapy. Methods: The NCDB collects data on approximately 75% of all newly diagnosed cancer cases annually in the U.S. We queried for all treatments in male and female (≥18 years old) TCC cases diagnosed between 1998 and 2003. Cancer stage (1998–2002) was forward converted to AJCC 6th edition. A total of 223,050 bladder and 11,625 UUT TCC cases were found. Results: Treatment patterns were analyzed in 11,328 patients with stage III bladder TCC and 1,840 patients with stage III UUT TCC, representing 5.0% and 15.8% of all cases, respectively (Table). Satisfactory follow-up was available for approximately 51% of patients. 5.4% (bladder) and 3.5% (UUT) of patients received pre-operative or adjuvant (within 4 mos of surgery) chemotherapy. No significant difference was seen comparing 1998 and 2003 perioperative chemotherapy use for bladder or UUT cancers. Conclusions: No increase in perioperative chemotherapy use occurred over the 5-year period (1998–2003), suggesting chemotherapy is underutilized in the management of surgically resectable stage III TCC of the bladder or UUT. This may reflect a delay in implementing the results of randomized trials recently reported or a low incidence of referral by urologists for perioperative chemotherapy. Further follow-up will determine if this pattern changes over the next 5 years. [Table: see text] No significant financial relationships to disclose.