bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative analysis of CT-scan and PET-scan with intraoperative ultrasound (IOUS) in detecting liver metastases
Authors: Patel M. , Saha S. , Sehgal R. , Gallardo L. , Doan K. , Berman B. , Wiese D. , Weiner S. , Arora M. , Singh T.
Published: March 2020

3632

Background: Open, laparoscopic or percutaneous radiofrequency ablation (RFA) has been used for the surgical treatment of liver metastases (mets). However, it requires accurate preoperative (preop) localization of liver mets. CT scan and PET scan have been widely used for such preop evaluation. However, intraoperative ultrasound (IOUS) remains the gold standard. Very little data is available comparing IOUS with preop CT and/or PET scan. Thus, a retrospective study was done to compare the efficacy of IOUS with preop CT and/or PET scan in detecting the number of liver mets. Methods: A retrospective chart review was done that included all patients (pts) who underwent surgical treatment for liver mets. Data was obtained from medical records, radiology, intraop reports. Results: 53 pts including 57% men and 43% women with a median age of 62years (age range 35–80 years) were included in the study. Imaging data was available for CT, PET and IOUS in 53, 24 and 39 pts respectively. CT, PET, and IOUS detected 2.4, 1.7 and 2.6 lesions/ pt respectively. In 24 patients, both CT and PET scan report was available. Of these, the imaging study detecting the maximum number of lesions was selected for comparison of preop evaluation with IOUS. A comparison between preop imaging (CT/PET scan) vs. IOUS in these 24 pts revealed an average of 2.3 vs. 2.8 lesions/pt respectively ( Table ). When compared with preop imaging (CT/PET scan), IOUS detected additional lesions in 33% pts; fewer lesions in 17% pts and similar number of lesions in 50% pts. Comparison between CT and IOUS in 39 patients revealed 1.9 vs. 2.6 lesions/pt respectively and that between PET and IOUS in 24 patients revealed 1.7 vs. 2.8 lesions/pt respectively. Conclusions: Although CT scan and PET scan remains effective modalities for preop evaluation of liver mets, IOUS is found to be superior for planning accurate surgical treatment. Thus, the efficacy of percutaneous RFA may be limited due to inability to perform IOUS.

[Table: see text]

No significant financial relationships to disclose.
A randomized clinical study of surgery versus radiotherapy in the treatment of resectable esophageal cancer
Authors: Yu J. , Ren R. , Sun X. , Yin Y. , Fu Z.
Published: March 2020

4013

Background: To compare the treatment results between radical surgery and late-course accelerated hyperfractionation radiotherapy (LCAHFR) for patients with resectable thoracic segment esophageal cancer. Methods: From June 1998 to September 2002, 269 patients with resectable thoracic esophageal cancer were randomized into two groups. 135 were with surgery and 134 with late-course accelerated hyperfractionated (LCAF) radiotherapy. Chemotherapy only for clinical recurrence and salvage therapy. Results: The 1-, 3- and 5- year overall survival rate were 88.6%, 56.2% and 34.7% in the surgery group and 93.3%, 61.5% and 36.9% in the radiotherapy group. There was no statistical difference between the two groups (P =0.58). Median survival was 28.5 months and 30.5 months respectively. The 1-, 3-and 5-year progression-free survival rate was 73.3%, 39.7% and 20.6% in the surgery group and 75.9%, 43.7% and 23.1% in the radiotherapy group (P =0.65) . There was no difference between the two groups in survival rates including different location and length (P > 0.05). The incidence of failure by hematogenous metastasis and distant lymphatic metastasis in the radiotherapy group (16.6% and 13.3% respectively ) was lower than in the surgery group ( 25.3% and 20.3 % respectively ), there was no significance between them. The incidence of local failure in the radiotherapy and surgery group was 57.3% and 27.8% respectively (P = 0.001) The incidence of death by local reasons was higher than in the surgery group (P = 0.02 ). The incidence of death by distant metastasis was lower than in the surgery group (P = 0.02 ). Conclusion: The treatment results between radical surgery and LCAHFR with conformal radiotherapy for patients with resectable thoracic esophageal cancer were comparable.

No significant financial relationships to disclose.
Vascular endothelial growth factor (VEGF) polymorphism is associated with prognosis of patients with gastric cancer
Authors: Chae Y. , Kim J. , Baek J. , Cho E. , Sohn S. , Chung H. , Yu W. , Lee M. , Bae H.
Published: March 2020

4019

Background: Recent studies demonstrated that the expression of vascular endothelial growth factor (VEGF) family had a prognostic significance in patients with gastric cancer. The present study analyzed VEGF polymorphism and its impact on prognosis in patients with gastric cancer. Methods: Five hundred three consecutive patients with surgically resected gastric adenocarcinoma at a single institution between January 2000 and December 2001 were enrolled into the study. Genomic DNA was extracted from paraffin-embedded tumor tissue and four VEGF (-460T > C, +405C > G, 936C> T, and -1154G > A) genotypes were determined using a PCR-RFLP assay. Results: The median age of patients was 60.0 years (range, 25–83 years), and 337 (67.0%) patients were male. Pathologic stages after resection were as follows: stage 0 (n=6, 1.2%), stage I (n=277, 55.1%), stage II (n=105, 20.9%), stage III (n=74, 14.7%), and stage IV (n=41, 8.2%). The estimated 5-year disease-free survival (DFS) rates according to stage were significantly different (p < 0.0001). Three VEGF polymorphisms (+405C > G, 936C, and -1154G > A > T) were not associated with survival of patients, while -460T > C polymorphism had a prognostic significance. In patients with early stage gastric cancer (stage 0 or 1, n=283), the estimated 5-year DFS and carcinoma-specific survival (CSS) for patients with homozygous genotype (CC or TT) of -460T > C were superior to those for heterozygous genotype (CT) (98.1% versus 90.3%, p=0.0047; 98.1% versus 92.5%, p=0.0284). In Cox multivariate regression, stage and VEGF -460T > C genotype were an independent prognostic factors for both DFS (p=0.007; p=0.010) and CSS (p=0.013; p=0.038). Conclusions: VEGF -460T > C polymorphism was found to be an independent prognostic marker for patients with curatively resected early stage gastric adenocarcinoma. Accordingly, VEGF -460T > C polymorphism can help to identify patients with unfavorable clinical outcome and thereby may be useful to refine therapeutic decisions in early stage gastric cancer.

No significant financial relationships to disclose.
Long-term follow-up and compilation of two trials utilizing concurrent paclitaxel/carboplatin/infusional 5-FU/radiation therapy (RT) in patients with localized esophageal cancer involved in the Minnie Pearl Cancer Research Network
Authors: Meluch A. A. , Greco F. A. , Spigel D. R. , Gray J. R. , Thomas M. , Meng C. , Bearden J. D. , Rosenoff S. H. , Hermann R. C. , Hainsworth J. D.
Published: March 2020

4028

Background: The role of preoperative chemoradiation in patients (pts) with localized esophageal cancer remains unclear. Most preoperative regimens produce 20–30% pathologic complete response (pCR) rates, which predicts improved survival. Our community-based multicenter group performed sequential trials evaluating a novel paclitaxel-containing preoperative chemoradiation regimen, now with median followup > 6 years. Methods: Eligibility: untreated adenocarcinoma or squamous carcinoma of esophagus or GE junction; clinical stage I-III; surgical candidate; ECOG PS 0–2, adequate organ function; informed consent. Pts received paclitaxel 200mg/m2 IV and carboplatin AUC 6.0 IV, days 1, 22; 5FU 225mg/m2, 24 hr continuous infusion, days 1–42; RT 45 Gy in 1.8 Gy/d single daily fractions. Surgical resection was performed 6–10 weeks after completion. Results: 226 pts with the following characterstics were treated: median age 58 years; adenocarcinoma 74%; distal/GE junction 79%; clinical stage II/III 84%. 220 pts (97%) completed preoperative therapy, and 199 pts (88%) had resection. Responses in resected pts: pCR 45% (39% of entire group), PR (microscopic residual) 29%, PR (macroscopic) 15%. After median followup of 75 months, median PFS and overall survival for the entire group were 19 and 26 months, respectively; 3- and 5-year survivals were 40% and 33%, respectively. Median survival was better in pts with pCR vs others (33 vs 21 mo; p=.026). 3-yr survival comparisons of other potential prognostic factors: adeno vs squamous, 43% vs 42%; clinical stage I vs II/III, 63% vs 36% (p=.001); distal location vs others, 38% vs 45% (p=.45). Toxicity data have been previously published; overall 13 pts (6%) had treatment-related death (preop 2, postop 11). Conclusions: This preoperative combined modality regimen was feasible and highly active in a community-based setting. This is one of the largest series of patients treated with an identical preoperative approach and with long-term followup is curative in one-third of pts with localized esophageal cancer.

[Table: see text]
Phase II study of cetuximab plus FOLFIRI as first-line treatment in patients with unresectable/metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (FOLCETUX study): Preliminary results
Authors: Pinto C. , Di Fabio F. , Siena S. , Cascinu S. , Rojas Llimpe F. L. , Ceccarelli C. , Mutri V. , Giaquinta S. , Piana E. , Martoni A. A.
Published: March 2020

4031

Background: Aim of this study was to evaluate efficacy and safety of cetuximab plus FOLFIRI as first-line treatment for advanced gastric or GEJ cancer. Methods: Eligibility criteria: histological diagnosis of stomach or GEJ adenocarcinoma, unresectable/metastatic/recurrent disease, EGFR+ (Dako), measurable disease, no prior chemotherapy for advanced cancer. Pts received cetuximab weekly at 400 mg/m2 iv loading dose, then at 250 mg/m2 iv, CPT11 180 mg/m2 iv d1, LFA 100 mg/m2 iv followed by 5FU 400 mg/m2 iv bolus and 600 mg/m2 iv continuous infusion 22h d1–2 (FOLFIRI) every 2 weeks, for a maximum of 24 weeks, then cetuximab alone was allowed in pts with CR/PR/SD. Objective response (OR) activity was assessed by CT and PET at baseline and after 6 weeks, and further by CT± PET every 6 weeks. Results: From November 2004 to December 2005, 49/54 (90.7%) screened subjects were EGFR+, and 38 pts were enrolled. Pt characteristics: 26 (68.4%) males, 12 (31.6%) females; median age 63.5 years (39–82); median KPS 90 (70–100); 34 (89.4%) stomach, 4 (10.5%) GEJ; 18 (47.3%) gastrectomy; 13 (34.2%) adjuvant chemotherapy; 4 (10.5%) locally advanced disease, 34 (89.4%) metastatic disease; main metastatic sites: 19 (50%) lymphonodes, 12 (31.5%) liver, 4 (10.5%) lung, 8 (21.0%) peritoneal. Median number of treatment weeks was: 10 (1–46). Median dose intensity was: 5FU 100% (25–100), CPT11 100% (25–100) and cetuximab 100% (80–100). At the present time, 25 pts are assessable for response and 28 for toxicity. The OR (RECIST) were: 3 (12%) CR,11 (44%) PR, e.g. 56% CR + PR (95% CI: 37–75), 11 (44%) SD. The PFS at 3 months is 80% (95% CI: 64–96). Survival data are premature (73.6% of the pts are alive; median follow-up 3 months, range 1–12). Grade 3–4 toxicity (CTC v3.0) was: 15 (53.6%) neutropenia (1 pt died of febrile neutropenia), 1 (3.4%) thrombocytopenia, 2 (6.8%) hypertransaminasemia, 1 (3.4%) hyperbilirubinemia. Cutaneous toxicity was: 7 (25%) gr1, 11 (39.2%) gr2, 5 (17.8%) gr3. Conclusions: Combination of cetuximab and FOLFIRI appears to be active in gastric and GEJ adenocarcinoma, with a high response and disease control rate. This treatment has been well-tolerated; the major toxicity is neutropenia.

No significant financial relationships to disclose.
Adjuvant chemotherapy with tegafur/uracil (UFT) for gastric cancer. A meta-analysis of centrally randomized clinical trials
Authors: Sakamoto J. , Tsuburaya A. , Morita S. , Matsui T. , Oba K. , Kodera Y. , Kobayashi M. , Yoshida K. , Nakao A.
Published: March 2020

4033

Background: A consensus regarding standard adjuvant chemotherapy for curatively resected gastric cancer has not been obtained between Japan and Western world. In order to evaluate the effect of UFT which is the most frequently used in Japan over surgery alone control, a meta-analysis was performed investigating 4 clinical trials. Methods: After meticulous examination of each trial, trials with improper randomization using envelop method were excluded from the analysis. A total of 1503 patients, enrolled in four relevant trials (JCOG 8401, JCOG 8801, JCOG9206–2, and NSAS-GC) using UFT for chemotherapy and performed by central randomization, were determined eligible for the meta-analysis. The endpoint was overall survival and intent-to treat analysis was implemented. Results: The 5-year overall survival odds ratio was 0.70 (95%CI; 0.54–0.89). The treatment effect of oral UFT was shown to be statistically significant (p=0.01) over surgery alone therapy (n=1251). No significant heterogeneity between the trials was demonstrated (p=0.365). The 5-year overall survival odds ratio was 0.71(95%CI; 0.54–0.92). Conclusions: From these results of the present meta-analysis, it is strongly suggested that chemotherapy after surgery with UFT, can improve survival of the patients with curatively resected gastric cancer, and UFT should be considered as the standard postoperative adjuvant treatment for gastric cancer in Japan, where extensive gastrectomy with D2 lymph node dissection is implemented as a routine surgical procedure.

No significant financial relationships to disclose.
Neoadjuvant and adjuvant chemotherapy without radiation for esophageal cancer
Authors: Ardalan B. , Spector S. , Livingstone A. S. , Franceschi D. , Ganjei-Azar P. , Lima M. , Sparling L. , Walker G. , Bowen-Wells C. P.
Published: March 2020

4054

Background: A Phase II trial to evaluate neoadjuvant (NAD) and adjuvant (AD) combination chemotherapy (CT) without radiation therapy (RT), for Stage III esophageal adenocarcinoma. Methods: Stage III disease by CAT scan or EUS and ECOG performance status 0–1. The CT cycles included Cisplatin, Taxol, FUDR and Leucovorin. The chemotherapy was given for 16 weeks prior to surgery, followed by adjuvant chemotherapy for patients whose pathology at the time of surgery demonstrated microscopic disease. Survival was estimated via Kaplan Meier. Results: 33 patients were enrolled: 28 completed NAD, 15 received AD. Of 33 pts given NAD, 16 had grade I/II toxicity and 14 had grade III/IV. In addition, 6 of 15 pts receiving AD had grade I/II toxicity and 3 had grade III/IV during that phase of treatment. Thirty-two (32) patients went to surgery, 30 patients were resected: 24 transhiatial and 6 transthoracic. Of the 28 patients who completed NAD, 19 (68%) demonstrated improvement in dysphagia; 11 (41%) gained weight, and 7 (26%) had no weight change. Pathologic response to NAD: 30 patients had partial response and 2 patients had progressive disease, one died prior to surgery, post carotid endarterectomy. Ten (10) patients showed no gross disease. Twenty-three (23) patients have expired, 17 disease related with distant metastasis, 1 with local recurrence and distant metastasis, 3 non-disease related and 2 unresectable cases. Kaplan-Meier estimates of overall survival at 1, 3, and 5 years were 73% (95% CI: 58 to 88%), 52% (95%CI: 34 to 69%), and 29% (95% CI: 13 to 45%), respectively. Median survival was 42 months (95% CI: 14 to 52 months). Ten (10) patients are alive after a median follow up of 73 months (range 45 to 89). Seven (70%) of the surviving patients received both NAD (2 cycles) and AD (1 to 2 cycles) and all had no evidence of disease as of last clinical and radiological evaluation. Conclusions: This regimen of combination CT for locally advanced esophageal adenocarcinoma is safe and comparable with those regimens that contain RT. There has been 1 local recurrence; 17 patients have recurred distantly. Omission of RT may allow for a more aggressive CT and reduction in the local complications post-surgery. This study needs to be confirmed in a larger phase II or in randomized phase III trial.

No significant financial relationships to disclose.
Phase II trial of preoperative (POP) irinotecan (I) + cisplatin (C) and radiotherapy for esophageal cancer
Authors: Visbal A. L. , Darling G. , Wong R. , Guindi M. , Hornby J. , Feld R. , Ringash J. , Keshavjee S. , Chen E. , Brierly J. , Knox J.
Published: March 2020

4056

Background: Esophagectomy (E) for locally advanced esophageal cancer (LAEC) yields limited survival; this phase II trial assess feasibility and efficacy of induction chemo-radiotherapy followed by E. Methods: Patients (pts) with LAEC of the thoracic esophagus (TE) or gastroesophageal junction (GEJ), ECOG PS ≤ 2 and surgical candidates underwent POP I (65mg/m2) + C (30mg/m2) on weeks 1,2,4,5,7,8 + concurrent conformal radiotherapy (40Gy/20 fractions (F) during wk 4–7) and external beam boost (10Gy/5F on wk 8); E was performed on wk 12–16 after restaging. Pts receiving 75% of POP chemotherapy were eligible for pathologic (p) evaluation; planned sample size 36 nonM1A pts. Results: 52 pts enrolled from 11/02 to 12/05, mean age 60 yr (33–79), male:40, GEJ:TE/15:37; 37 adenocarcinoma, 13 SCC, 2 other; 13 pts were stage IIA, 7 IIB, 22 III, and 10 IVA. Toxicity during POP treatment included ANC (G3/4:36%), febrile neutropenia (9%), diarrhea (G3:9%), nausea (G3:6%), esophagitis (G3:2%) and anorexia (G3/4:15%); 3 pts stopped treatment due to toxicity, 2 withdrew, 2 progressed becoming non-operable, 1 died of a stroke and 1 from central line sepsis. Clinical response by RECIST was CR:2%, PR:30%, SD:62% and PD in 6%. Dysphagia improved or resolved in 34/47 pts (72%) during POP treatment. Of 43 evaluable pts, 41 underwent E, achieving R0 resection in 98% (1 refused E, 1 pending). Perioperative complications included anastomotic leak (23%), Afib (21%), pneumonia (21%), delirium (10%) and aspiration (10%); 1 pt died from aspiration. 7 pts (17%) achieved pCR, 2 of whom were pretreatment clinical stage IIA, 1 IIb and 4 III; downstaging occurred in 3/7 pts; 15 pts (36.6%) achieved minimal residual disease, 15 (36.6%) pPR, and 4 (9.8%) pSD. At a median (med) follow-up of 15.2 months (1.3–34.5m), 16/52 patients died (med & 2yr overall survival (OS) of 29 m & 66%). Of 41 resected pts, 17 recurred (med & 2yr disease free survival (DFS) of 20m & 46%) of whom 10 died of progression (med & 2-yr OS of 29m & 68.4%). 2yr DFS & OS was 83% & 86% in pCR vs 41% & 76% in non-pCR. Conclusion: In LAEC, induction I/C and radiotherapy followed by E is associated with 72% dysphagia improvement, a significant but manageable toxicity profile, and encouraging survival compared to historical controls.

[Table: see text]
Preoperative oxaliplatin (O), docetaxel (D), capecitabine (C), and concurrent radiation therapy (RT) for patients (pts) with localized esophageal cancer: A phase I/II trial of the Minnie Pearl Cancer Research Network
Authors: Barnes E. K. , Spigel D. R. , Greco F. A. , Meluch A. A. , Yardley D. A. , Burris H. A. , Shipley D. L. , Patton J. F. , Farley C. , Hainsworth J. D.
Published: March 2020

4058

Background: Preoperative chemoradiotherapy improves outcomes for pts with resectable esophageal cancer compared with surgery alone. We previously reported a 41% 3-year progression-free survival (PFS) with preoperative paclitaxel/carboplatin/5FU/RT in a large phase II trial. The present multicenter community trial examined the role of a newer combination regimen. Methods: The primary endpoints were to assess the safety and response rate (RR) of O/D/C/RT in pts with resectable stage I-III cancer of the mid-/distal-esophagus or GE junction. Treatment (tx): O 40 mg/m2 IV and D 20 mg/m2 IV weekly x 5; C 1000 mg/m2 PO BID D1–7, 15–21, 29–35; and RT 45 Gy, 1.8-Gy M-F weekly x 5, starting D1. Pts were resected 4–8 weeks after tx. The phase I portion (n=10) confirmed the safety of O/D/R, and C was added in the phase II portion. Eligibility: measurable disease; ECOG PS 0–1, informed consent. Analysis was by intent to treat. Results: Nineteen pts were enrolled from 9/04 to 10/05 (trial ongoing). Baseline features: median age 60 years (38–77); male/female, 82%/18%; ECOG PS 0/1: 27%/73%; adenocarcinoma/squamous (77%/23%); I (5%), IIA (5%), IIB (33%), III (38%), primary tumor not assessable (19%). All pts completed O/D/C/RT and 14 (74%) were resected. Grade (G) 3/4 non-hematologic toxicity: anorexia (16%), nausea (16%), and fatigue (11%). Other G3/4 non-hematologic toxicities were ≤5%, with no G3/4 esophagitis. No G3/4 hematologic toxicities or tx-related deaths occurred. Complete/partial responses assessed before surgery were seen in 2 pts/11 pts, respectively, for an overall RR of 68% (95% CI 46%-84%). Four pts (21%) had stable disease and 1 pt had progression (1 pt was unevaluable). Pathological complete responses were seen in 8 of 14 evaluable pts (57%). With a median follow-up of 8 months, actuarial 1-year PFS and overall survival (OS) are 66% and 79%, respectively. Median PFS and OS have not been reached. Conclusions: O/D/C/RT is a relatively well-tolerated and active preoperative therapy for pts with resectable esophageal cancer. Additional pts and follow-up are needed to assess this regimen’s benefits.

[Table: see text]
Efficacy of patupilone in advanced local or metastatic gastric cancer: A phase IIa trial
Authors: Hsin K. W. , Boyer M. , Ducreux M. , Liu M. , Soo R. , Yeo W. , Williams K. J. , Johri A.
Published: March 2020

4069

Background: Although the use of taxanes has produced encouraging response rates in patients with advanced local or metastatic gastric cancer, outcomes remain unsatisfactory. Patupilone (EPO906; epothilone B), a novel microtubule stabilizer, has demonstrated anti-tumor activity against a broad range of tumors in vitro and in animal models. The present trial evaluated the efficacy of patupilone in patients with locally advanced or metastatic gastric cancer. Methods: Patients with confirmed gastric adenocarcinoma (defined by RECIST) received patupilone 2.5 mg/m2/wk by single 5- to 7-minute IV infusion for 3 weeks, followed by 1 week off (4-week cycle). Additional inclusion criteria: WHO performance status ≤2, age ≥18 years, life expectancy ≥3 months, and no major hematologic, renal, or hepatic impairment. The primary objective of this open-label, single-arm, 2-stage, multicenter study was to determine the objective response rate (using RECIST) of treatment with patupilone in this population. Results: All 22 patients enrolled were evaluable. Mean age was 61.1 years, 63.6% were men, and 72.7% were oriental. Of 18 patients (81.8%) who completed the study, 10 (45.5%) had disease progression and 8 (36.4%) died from the disease; of 4 discontinuations, 3 were due to adverse events (AEs) and 1 to abnormal alkaline phosphatase. Overall response: 2 patients had partial responses, 6 disease stabilization, 12 disease progression, and 2 unknown. The duration of response in the 2 partial responders was 176 and 113+ days, with the latter censored at 113 days. The most frequently reported AEs were diarrhea (n = 18), nausea (n = 14), vomiting (n = 13), abdominal pain (n = 10), and fatigue (n = 10). Of these AEs, 9 were grade 3 (4 diarrhea, 3 vomiting, 1 nausea, and 1 fatigue) and 2 were grade 4 (1 nausea and 1 vomiting). Grade 4 AEs also included 1 gastric outlet obstruction and 1 dehydration. Conclusions: Patupilone resulted in an overall tumor response/disease stabilization rate of 36.4%, was well tolerated, and may prove to be a viable alternative to taxane treatment in advanced local/metastatic gastric cancer.

[Table: see text]
Oxaliplatin and irinotecan chemotherapy in advanced gastric cancer. Final results of a multicenter phase II trial
Authors: Woell E. , Kühr T. , Eisterer W. , Gattringer K. , Greil R. , Zabernigg A. , Hilbe W. , Thaler J.
Published: March 2020

4070

Background: There are only limited treatment options for advanced gastric cancer. Development of new treatment options is therefore warranted. The aim of this study was to evaluate the safety, feasibility and efficacy of an outpatient Oxaliplatin/Irinotecan combination in patients suffering from unresectable, locally advanced and/or metastatic gastric cancer. Methods: The combination of Oxaliplatin 85 mg/m2 biweekly with Irinotecan 125 mg/m2 biweekly was chosen since it has been shown in colorectal cancer that a biweekly dose of at least 85 mg/m2 oxaliplatin is superior to a lower dose and toxicity of Irinotecan is much lower if given fractionated into two doses. Furthermore the Irinotecan dose below MTD considers concerns about increased toxicity in gastric cancer patients. Results: 43 patients with histologically proven unresectable and/or metastatic gastric adenocarcinoma and no previous palliative chemotherapy and/or immunotherapy were selected. Median age: 61 years (range 32–81 years), male/female ratio: 24/19, PS 0:11 patients, PS <3:32 patients, locally advanced cancer 5 patients, single metastatic site: 19 patients, multiple metastases: 19 patients, previously adjuvant radiochemotherapy: 4 patients. This outpatient regimen was generally well tolerated. Frequently reported adverse events (more than 20% of patients) were grade 1 or 2 and included neutropenia (44% of patients), thrombocytopenia (30%), anemia (77%), nausea 67%), diarrhea (51%), alopecia (35%). Grade 3 and 4 toxicities included neutropenia in 2/43 pts., anemia in 3/43 pts., nausea in 2/43 pts., and diarrhea in 4/43pts. 5 patients were taken off-study due to toxicity (asthenia, nausea, reversible renal failure, diarrhea). Sensory neuropathy occurred only as grade 2 in 14%, no grade 3/4 neurotoxicity was observed. For response 38 patients are assessable with 3 pts. (8%) showing a CR, PR in 19 pts. (50%), SD in 11 pts. (29%), PD in 5 pts. (13%). Median TTP was 5.3 months and median OS 9.5 months. Conclusions: The outpatient combination of a biweekly Oxaliplatin/Irinotecan chemotherapy is well tolerated and shows a response rate within the range of other combination therapies. The favourable toxicity profile makes it an alternative 1st line regimen.

[Table: see text]
Incidence of thromboembolic events (TEEs) before and during chemotherapy of patients with advanced gastric and gastroesophageal junction carcinoma (AG-GEJC) on clinical trials
Authors: Tetzlaff E. D. , Baker J. , Ajani J. A.
Published: March 2020

4073

Background: TEEs are associated with AG-GEJC and chemotherapy can further increase its incidence. We assessed TEEs before and during protocol chemotherapy for AG-GEJC patients. Methods: Patients with AG-GEJC on four approved protocols between August 1997 and September 2003 were assessed for baseline TEEs, new TEEs during therapy, histology, location of the primary, and overall survival. Three protocols evaluated camptothecin-based chemotherapy (irinotecan, peg-camptothecin, and rubitecan) and one evaluated non-camptothecin-based chemotherapy. Results: We studied 191 patients. Median age was 56 (range 20–80), Male:Female 151:40, chemotherapy naïve 132 (69%). 136 patients received irinotecan-based therapy and 55 patients received non-camptothecin-based therapy. Overall, TEEs occurred in 13.6% of patients. At baseline, TEEs were diagnosed in 5.3% of untreated patients and were diagnosed in 8.5% of patients with one prior chemotherapy regimen. During protocol therapy, TEEs occurred in 6.8% of untreated patients and 10.2% of previously treated patients. The most common TEE during protocol treatment was deep vein thrombosis (46.7%). First-line camptothecin-based chemotherapy was associated with TEEs in 6.5% of the patients. Non-camptothecin-based chemotherapy was associated with TEEs in 7.3% of the patients. Untreated patients receiving irinotecan plus cisplatin had the lowest incidence of TEEs (2.6%) during treatment. TEEs increased to 10.3% in second-line therapy with irinotecan plus cisplatin. Age, gender, location of the primary tumor, and histology did not differ between patients with or without a TEE during treatment. Survival data was available for 67 patients. The median survival of patients with a TEE at anytime was 3.7 months while it was 8.1 months for patients with no history of TEE. Conclusions: This is the first report describing TEEs at baseline and during chemotherapy for patients with AG-GEJC treated on chemotherapy protocols. The data show that chemotherapy is associated with higher risk of TEEs and TEEs influence survival.

No significant financial relationships to disclose.
Circulating dendritic cell as a new prognostic factor in pancreatic cancer patients
Authors: Satoi S. , Yanagimoto H. , Takai S. , Toyokawa H. , Takahashi K. , Terakawa N. , Yamamoto T. , Kamiyama Y.
Published: March 2020

4095

Background: Pancreatic cancer is a cancer with very poor prognosis that might be associated with impaired immune defense. Dendritic cells (DC) are important for immune surveillance and play a central role in protection against infection and malignancy. A defective host antitumor immune response may allow tumor cells to escape from the host immune system. The aim of this study is to determine whether circulating DC could be one of new immunological markers that may predict the prognosis of the pancreatic cancer. Methods: We evaluated pretreatment circulating myeloid-lineage DC (C-DC1) rate in the peripheral blood mononuclear cell and various clinical parameters to determine their prognostic value in 104 pancreatic cancer patients (41 resected and 63 unresected patients) seen at our institution. Results: In unresected patients, univariate analysis demonstrated two risk factors for prognosis of albmin < 3.8g/dl (p = 0.0468), and C-DC1 < 0.27% (p = 0.0006), when all patients were divided by the median value of C-DC1 rate. Consequently, multivariate analysis demonstrated that only C-DC1 was a predominant independent predictor of survival (Hazard ratio; 9.330, 95% Confidential interval; 2.595–33.549, p = 0.0006). In resected patients, C-DC1 in patients with advanced disease (Stages 2b-4, n=28) was significantly lower than that in patients with lower staged cancer (Stage 1–2a, n = 13: 0.43 ± 0.67%, Stage 2b-4: 0.24 ± 0.30%, p < 0.05). The overall survival rates in patients with C-DC1 ≥ 0.27% were significantly longer than those in patients with C-DC1 < 0.27 (C-DC1 ≥ 0.27%, n = 20, 1/3 year survival: 100%/64%. C-DC1 < 0.27, n = 21, 1/3 year survival: 68%/26%. P < 0.05). Conclusions: The C-DC1 less than 0.27% could be one of prognostic factors in patients with pancreatic cancer, and such patients could be targets for the future therapeutic trials.

No significant financial relationships to disclose.
A phase I study of oxaliplatin, full-dose gemcitabine and concurrent radiation therapy in patients with pancreatic cancer
Authors: Desai S. P. , Ben-Josef E. , Lawrence T. J. , Francis I. R. , Greenson J. K. , Alfred C. E. , Colletti L. M. , Simeone D. M. , Normolle D. P. , Zalupski M. M.
Published: March 2020

4107

Background: We previously demonstrated safety and efficacy of full dose gemcitabine (GEM) and radiation therapy (RT) in patients (pts) with pancreatic cancer (PC). Our preclinical studies have shown that GEM with oxaliplatin (OX) preserves radiosensitization with synergistic cytotoxicity. To enhance local and systemic treatment effects, we initiated a study of OX and GEM with concurrent RT. Methods: Pts with untreated PC received up to 4 cycles of GEM day 1, 8, 15 and OX days 1, 15 repeated at 28 day intervals. RT (27 Gy in 1.8 Gy fractions to gross tumor volume with 1 cm margin) was given during cycle 1 and repeated in cycle 4. Surgery occurred after cycle 2 in resectable pts. Dose escalation was guided using time-to-event continuous reassessment method (TITE-CRM). Dose levels 1–4 GEM 1 g/m2 IV over 30 min and OX 40, 55, 70, 85 mg/m2 IV over 90 min; dose level 5, 6 OX dose remained 85 mg/m2 but infusion time for GEM 1 g/m2 was increased to 65, 100 min, respectively. Trial objective is to determine dose level associated with DLT thru cycle 2 in ≤ 20% of pts; planned accrual is 40 pts evaluable for DLT. Results: 40 pts have been enrolled (median age 63, men/women 26/14) with resectable (10), unresectable (27), and metastatic (3) PC. 29 pts have completed 2 cycles and 11 pts 4 cycles. After 2 cycles CA19–9 decreased > 50% in 14 of 24 evaluable pts (58%). Six of 8 explored pts underwent margin negative resection with 1 path CR and 2 with small residual microscopic foci only. Per RECIST, CT response of the primary lesion after 2 cycles included 3 PR, 23 SD and 1 PD. Two additional PR were seen after cycle 4. Thirty pts are presently evaluable for DLT; 7 pts have suffered DLT including grade 4 platelets (4), decline in PS (2), GI bleed (1) and grade 3 weight loss (1). Current estimated probability of DLT is 21% (95% CI 11%,34%) for dose level 3 and 24% (95% CI 13%,37%) for dose level 4. Conclusions: The addition of OX 70–85 mg/m2 days 1, 15 to full dose GEM based RT is tolerable and efficacious. A neoadjuvant phase II study in resectable PC using the MTD defined in this phase I study is planned. Supported by Sanofi-Aventis.

[Table: see text]
A phase II trial of oxaliplatin plus capecitabine (xelox) as second line therapy for patients with advanced pancreatic cancer
Authors: Xiong H. Q. , Wolff R. A. , Hess K. R. , Varadhachary G. R. , Blais J. C. , Abbruzzese J. L.
Published: March 2020

4119

Background: There is no established chemotherapy for patients with pancreatic cancer who have progressed on gemcitabine. This trial was designed to explore the efficacy of xelox as second line therapy in patients with pancreatic cancer. Methods: The primary objective was to determine overall survival at 6 months. It was estimated that 40 patients would be needed to detect 50% 6-month survival with 90% credible interval between 37%-62%. Eligibity criteria included biopsy-confirmed diagnosis of adenocarcinoma of the pancreas, one prior systemic chemotherapy, ECOG performance status (PS) 0–2, and adequate hepatic, renal, and bone marrow functions. Oxaliplatin was administered at 130 mg/m2 and capecitabine at 1000 mg/m2 twice daily for 14 days for patients who were younger than 65 and had ECOG PS score 0–1. For patients older than 65 or PS 2, the oxaliplatin dose was decreased to 110 mg/m2 and capecitabine to 750 mg/m2/twice daily. The treatment was repeated every 3 weeks. Tumor measurements were performed every 9 weeks (3 cycles) in patients who had measurable disease by RECIST criteria, although measurable disease was not required. Results: A total of 41 patients were enrolled into the study, 2 were never treated. Among 39 evaluable patients, 17 were female, median age 62 years (45–75), and 8 had ECOG PS 2. For the 36 patients who have completed therapy, the median number of treatment cycle was 3 (range, 1–6). Grade 3 or 4 toxicities included: abdominal pain (2 patients), dehydration (3), diarrhea (2), fatigue (6), gastrointestinal syndrome (including diarrhea and colitis) (4), hand-foot syndrome (1), hematemesis (1), mastitis (1), myocardial infarction (1), nausea/vomiting (2), neuropathy (1), non-neutropenic fever (1), pneumonia (1). One patient had a partial response and 8 others had stable disease. Median survival duration was 5.8 months (95% confidence interval [CI] 3.2–12.1 months). The six month and 1 year survival rate was 48% (95% CI 33%-70%) and 22% (95% CI 9%-51%), respectively. Conclusions: When used in the second line setting, the xelox has promising activity in pancreatic cancer.

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Phase II study of gefitinib and docetaxel as salvage therapy in patients (pts) with advanced pancreatic adenocarcinoma (APC)
Authors: Shadad F. , Matin K. , Evans T. L. , Volkin R. L. , Kiefer G. J. , Schlesselman J. J. , Cai C. , Schmotzer A. , Dranko S. , Ramanathan R. K.
Published: March 2020

4120

Background: There is no standard-of-care second-line chemotherapy for APC. The combination of docetaxel and gefitinib, an inhibitor of epidermal growth factor receptor (EGFR) shows enhanced preclinical activity compared to docetaxel alone. Docetaxel alone has activity in APC, and this phase II trial is designed to evaluate the combination. The primary endpoint is survival with an accrual goal of 45 patients to detect an improvement to 5.25 months (mo) in median survival time by one-sided log-rank test at level α = 0.05. Methods: Patients with APC and one prior chemotherapy regimen are eligible for study; EGFR over-expression is not required. Gefitinib is administered at the dose of 250 mg/day orally without interruption. The initial dose of docetaxel was 75 mg/m2 every three weeks (one cycle), but was reduced to 60 mg/m2 due to a high incidence of febrile neutropenia. Results: 31 pts, all with prior gemcitabine therapy, have been enrolled on study to date, with 26 evaluable for toxicity. Patient characteristics: 62% male; 92 % with ECOG performance status 0/1, 8% ECOG of 2; median age 64 years (range 47–82 years). The best response is stable disease (5 pts), median cycles administered 2 (range 1–12). Thus far the median survival time is 4.4 mo, with median time to progression of 2.5 mo. Grade (G) 3/4 febrile neutropenia occurred in 8 out of 18 pts treated at the 75 mg/m2 dose of docetaxel; none has been seen with the 60 mg/m2 dose. Other G 3/4 adverse events include: diarrhea (3.8%), rash (7.7%), constitutional symptoms (11.5%), and nausea (11.5%). Conclusion: The combination of gefitinib and docetaxel at 60 mg/m2 is tolerable, with interim results showing a median survival time of 4.4 mo at this point. If the protocol’s goal of median survival time of 5.25 mo is met upon study completion, the combination may be worthy of further investigation.

No significant financial relationships to disclose.
A phase I study of the VEGF receptor tyrosine kinase inhibitor vatalanib (PTK787/ZK 222584) and gemcitabine in patients with advanced pancreatic cancer
Authors: Kuo T. , Fitzgerald A. , Kaiser H. , Sikic B. I. , Fisher G. A.
Published: March 2020

4122

Background: The VEGF pathway is the predominant mediator of angiogenesis in pancreatic cancer. Vatalanib (PTK787/ZK 222584) is a small molecule tyrosine kinase inhibitor of all known VEGF receptors. We initiated a phase I study of vatalanib and gemcitabine for advanced pancreatic cancer. Methods: Patients with newly diagnosed unresectable or metastatic pancreatic adenocarcinoma were enrolled. Previous adjuvant chemoradiotherapy with fluorouracil was allowed. Gemcitabine was given by fixed-dose rate infusion weekly x 3 in a 28-day cycle, and vatalanib was given orally daily. Dose-limiting toxicities (DLT) are defined as any grade 3/4 toxicity during the first cycle. The dose levels are as follows: Results: To date, 11 patients are evaluable for toxicity (5M/6F; median age 62 years, range 40–82 years; median KPS 90%). Thus far, 42 cycles have been given, with a median of four cycles per patient. Two patients have experienced DLT. The first patient (cohort 1) experienced grade 3 diarrhea and hypokalemia and grade 4 neutropenia occurring simultaneously and treated without sequelae. The second patient (cohort 3) developed grade 3 deep vein thrombosis. Beyond the first cycle, grade 3 toxicities included neutropenia (1), anemia (3), thrombocytopenia (1), hypertension (2), diarrhea (1), hypokalemia (1), thrombosis (1), and proteinuria (1). Three of eleven patients (27%) did not complete treatment to the first evaluation timepoint (2 cycles); two discontinued due to toxicity and one discontinued due to disease progression. Two of eleven patients (18%) had a partial response by RECIST. Six of eleven patients (55%) had stable disease as the best response ranging from 2–6 months. Conclusions: The combination of gemcitabine and vatalanib is generally well-tolerated with most grade 3/4 toxicities occurring late in the treatment course. Antitumor responses have been observed at initial dose levels and accrual to the final cohort with BID dosing of vatalanib continues.

[Table: see text]

No significant financial relationships to disclose.
Current status of targeted agents in advanced pancreatic cancer (APC): A pooled analysis of 2,361 patients (pts) enrolled in six phase III trials
Authors: Bria E. , Carlini P. , Gelibter A. , Ruggeri E. , Ceribelli A. , Pino M. , Terzoli E. , Cognetti F. , Giannarelli D. , Milella M.
Published: March 2020

4126

Background: Molecular targeting of pathways that are deregulated in pancreatic cancer is a promising approach aimed at improving the dismal prognosis of APC pts. However, the clinical impact of novel “biological” drugs (ND) remains to be defined. Methods: All prospective phase III trials comparing single-agent Gemcitabine (G) with either a ND or a combination of ND and G (ND+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: Six trials involving 2361 pts were identified; ND tested included: FTI inhibitors (1 trial), MMP inhibitors (3 trials), EGFR inhibitors (1 trial), and anti-gastrin vaccine (1 trial). The analysis was conducted considering three different subgroups: 1) overall population (2361 patients, 6 trials), 2) ND+G vs G (1879 patients, 4 trials), and 3) ND vs G (482 patients, 2 trials). As shown in the table, no significant differences in either the primary outcome (OS) or the secondary outcome of PFS were observed in the overall population as well as in ND+G vs G trials, while a significant negative trend for ND was found in ND vs G trials with regard to both endpoints. Conversely the evaluation of the secondary endpoint of ORR significantly favored G in the overall population as well as in ND vs G trials, while a not significant negative trend for ND was observed in ND+G vs G trials. Conclusions: G remains the treatment of choice in APC pts. The ND tested, either alone or combined with G, do not seem to add any benefit over G. A better understanding of pancreatic cancer biology and further clinical evaluation of new agents and is needed to improve prognosis in APC pts.

[Table: see text]

No significant financial relationships to disclose.
Improvement of survival in VA patients with gall bladder cancer given chemotherapy
Authors: Atiq M. , Safa M. M. , Komrokji R. S. , Jazieh A. R. , Muhleman A. F. , Nahleh Z. A. , Pancoast J.
Published: March 2020

4132

Background: Gallbladder carcinoma, though rare, has very poor prognosis. Most of patients with gall bladder carcinoma present with either unresectable disease or metastasis. Median survival in gall bladder carcinoma has been documented to be 6 months in SEER data. There is no data available on the outcome of Veterans’ Affair (VA) patients with gall bladder carcinoma. Impact of chemotherapy in adjuvant and metastatic setting is not well-studied. Methods: We used the VA Central Cancer Registry (VACCR) to analyze VA patients with Gall Bladder cancer diagnosed between 1995 and 2005. The reference date for data collection and reporting is January 1, 1995. This site aggregates the data collected by the medical centers’ cancer registries. Data was entered and analyzed using bio-statistical software SPSS. Results: There were a total of 232 patients. Of these, 185 (79.7%) were whites and 37 (15.9%) were blacks. The mean age was 71 years. Pathology was adenocarcinoma in 198 (85.3%), non-specified carcinoma in 29 (12.5%) and small cell carcinoma in 5 (2.2%) cases. Overall median survival was 5.27 months. Surgery was performed in 119 patients (51%). Only 19 (16%) patients received adjuvant chemotherapy. The baseline characteristics were similar between patients who received adjuvant chemotherapy and no adjuvant chemotherapy. Also, the median survival was similar (8.3 months vs. 8.7 months) (P-value 0.37). In patients who did not undergo surgery, the median survival for patients who received chemotherapy was 8.0 months vs 1.7 months for patients who did not receive chemotherapy (p-value 0.013). Eighty-nine (38.5%) patients were diagnosed with stage IV disease. Amongst these patients chemotherapy improved the median survival (2 months vs. 6.97 months; p-value 0.04). In a Cox regression model stage, surgical margins, surgery, chemotherapy were independent predictors of patient survival. Conclusions: Gall bladder carcinoma in VA patients has similar survival compared to other reports. Our data is one of the largest retrospective cohorts in gall bladder cancer and suggests that chemotherapy improves survival in advanced gall bladder cancer patients.

No significant financial relationships to disclose.
SWOG S0202: A phase II trial of gemcitabine and capecitabine in patients (pts) with unresectable or metastatic gallbladder cancer or cholangiocarcinoma
Authors: Iqbal S. , McCoy S. , Lenz H. J. , Rivkin S. E. , Atkins J. N. , Blanke C. D.
Published: March 2020

4134

Background: Pts with gallbladder cancer or cholangiocarcinoma usually present with advanced disease and limited treatment options. Based on data demonstrating effectiveness of gemcitabine in pancreatic carcinoma and the common embryologic origin of the exocrine pancreas and gallbladder, this trial was pursued. The primary objective of this study was to assess the response rate (confirmed complete and partial responses). Secondary objectives included overall survival and toxicities for gemcitabine and capecitabine. Methods: A two-stage design was used to detect a difference in the null hypothesis of 5% response probability and the alternative 20% response probability. If at least one response occurred after the first 20 pts, another 20 were to be accrued. The combination of gemcitabine 1,000 mg/m2 IV over 100 minutes days 1, 8 and capecitabine 650 mg/m2 BID PO days 1–14, was administered every 21 days. Results: The study accrued 57 pts from September 2003 until April 2005. Three patients were ineligible, and two others received no treatment. Characteristics of analyzable pts: 35 (73%) cholangiocarcinoma, 17 (32%) gallbladder cancer; PS 0 (18 pts), 1 (26 pts), 2 (8 pts); 26 (50%) male; median age 58.8 years (29.5–85.6). Among 51 pts evaluated for toxicity, 6 experienced grade 4 toxicities: 1 thrombosis/embolism and muscle pain, 1 fatigue and 4 neutropenia, one of whom also had grade 4 leukopenia and grade 4 anemia. Among 52 pts, there were 5 confirmed partial responses for a confirmed response probability of 10% (95% CI 3% to 21%). Four pts had an unconfirmed partial response for an overall response probability of 18% (95% CI 8% to 30%). Fourteen patients (27%) stable disease. The 6 month overall survival was 56% (95% CI 42%–70%) and median survival was 7.0 months. Conclusions: Gemcitabine and capecitabine is a well tolerated regimen with activity in pts with advanced gallbladder cancer and cholangiocarcinoma. Correlative analyses are ongoing.

[Table: see text]