bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bevacizumab 5mg/kg can be safely infused over 10 minutes
Authors: Reidy D. L. , Chung K. Y. , Timoney J. P. , Park V. , Hollywood E. , Sklarin N. , Muller R. , Saltz L. 
Published: March 2020

4135 Background: Bevacizumab is a humanized monoclonal antibody that targets VEGF. Due to concerns for potential infusion- related hypersensitivity reactions (HSRs), initial phase I trials used an initial 90, 60, 30 minute infusion sequence. We sought to determine if the initial prolonged infusion was still necessary and in addition, if, on the basis of available clinical experience, an infusion time of less than 30 minutes could be safely used. Methods: We used computerized pharmacy records to identify all patients who received bevacizumab at our institution in the first two years of commercial availability (2/1/04- 6/30/06). Our institutional adverse drug reaction reporting program was utilized to identify any infusion reactions possibly related to bevacizumab and patient medical records were reviewed for confirmation Results: A total of 1,077 patients were treated with 10,606 doses of bevacizumab, and 765 of these patients received a 5 mg/kg dose (total of 8,494 doses). No HSRs occurred with the 90, 60, 30 minute infusion sequence in the first 202 patients. The standard infusion rate was then modified to 30 minutes for all bevacizumab doses. No HSRs were encountered. The infusion was again modified to a rate of 0.5 mg/kg/min. Of the 370 patients who received a total of 2,311 doses of bevacizumab at 5 mg/kg over 10 minutes, six (1.6 %) experienced events of minor clinical consequence that were felt to be possibly consistent with non-serious HSRs Conclusions: 90 and 60 minute initial infusion times are unnecessary. Use of a standard infusion rate of 0.5 mg/kg/min is safe, logical, justifiable, and is the current policy at our institution. No significant financial relationships to disclose.
Phase II study of RAD001 (everolimus) and depot octreotide (sandostatin LAR) in advanced low grade neuroendocrine carcinoma (LGNET)
Authors: Yao J. C. , Phan A. , Chang D. Z. , Wolff R. A. , Jacobs C. , Mares J. E. , Gupta S. , Meric-Bernstam F. , Rashid A. 
Published: March 2020

4503 Background: Effective systemic therapy for advanced LGNET is lacking. Mutations involving the mTOR pathway including TSC2, NF-1, and vHL are associated with development of LGNET. mTOR also mediate signaling downstream of IGF1 and VEGF. RAD001 is a novel oral mTOR inhibitor. Octreotide has been described to inhibit VEGF and IGF1 production in solid tumors. Methods: Patients (pts) received depot octreotide 30 mg q28 days, and RAD001 5 (pts 1–30) or 10 mg (pts 31–60) po daily. Response was evaluated every 12 weeks (wks). Results: 30 carcinoid (C) and 30 islet cell (I) patients (pts) were enrolled between 2/05–7/06. 38 pts (23 C, 15 I) had prior octreotide. By RECIST criteria, there were 10 PR (17%), 45 SD (75%) (15 pts had > 15% reduction), 5 PD (8%). The response rates within C, and I groups were 13% and 20%. The response rates within the 5 mg and 10 mg groups were 13% and 20% respectively. Of 39 pts with PD prior to study entry, there were 7 (18%) PR, 27 (69%) SD (9 pts had > 15% reduction), 5 (13%) PD. PFS rate at 24 wks was 86%. The median PFS duration is 59 wks. The median PFS duration among the C and I groups were 69 and 39 wks. Among the 39 pts with progression at study entry, the median PFS duration was 38 wks. Of 24 pts with elevated chromogranin A at entry, 19 (56%) had > 50% reduction. Treatment was well tolerated. The most common toxicity was mild aphthous ulceration. CTC G3/4 toxicities included: thrombocytopenia (3), neutropenia (3), hypophosphatemia (5), hyperglycemia (4), hypoglycemia (2), hypokalemia (2), fatigue (6), diarrhea (6), aphthous ulcer (5), rash (3), and 1 each of anemia, hypertriglyceridemia, bilirubin, AST/ALT, pain, nausea, nail, dysgeusia, pneumonitis. Conclusions: RAD001 at 5 or 10 mg daily was well tolerated in combination with octreotide. Promising anti-tumor activity has been observed. The RADIANT (RAD001 In Advanced Neuroendocrine Tumors) trials are underway to evaluate RAD001 in larger patient groups. No significant financial relationships to disclose.
Preoperative chemotherapy (CTX) versus preoperative chemoradiotherapy (CRTX) in locally advanced esophagogastric adenocarcinomas: First results of a randomized phase III trial
Authors: Stahl M. , Walz M. K. , Stuschke M. , Lehmann N. , Seegenschmiedt M. H. , Riera Knorrenschild J. , Langer P. , Bieker M. , Königsrainer A. , Budach W. , Wilke H. 
Published: March 2020

4511 Background: Perioperative treatment is common in localized adenocarcinomas of the upper GI-tract. By now, there is no randomized data about the contribution of preoperative radiotherapy additional to chemotherapy. Methods: Based on phase II results of our group we targeted 394 patients to test whether chemoradiation will increase the 3-year survival rate by 10% compared with chemotherapy. Patients with stage T3–4 NX M0 according to EGD, EUS, CT and laparoscopy were included. Patients were randomized to treatment with either (arm A) 2.5 courses of chemotherapy (cisplatin 50mg/m2, d 1,15,29, folinic acid 500 mg/m2 and 5-FU 2g/m2 24h-infusion, weekly times 6, qd 49 or (arm B) 2 courses of the same chemotherapy followed by three weeks of chemoradiotherapy (30 Gy, cisplatin 50 mg/m2 d 2+8 and etoposide 80 mg/m2 d 3–5). Epoetin alpha was recommended to keep the hemoglobin above 12.5 g/dl. Tumor resection was planned 3 to 4 weeks after the end of preoperative therapy for both groups. Results: A total of 126 patients were randomized into the study between 12/00 and 12/05 when the trial was closed due to poor accrual. 120 pts. were eligible (CTX 60, CRTX 60). The toxicitiy of CTX was low. Severe leucocytopenia and thrombocytopenia was 35% and 16%, respectively during CRTX. Until 12/06 ninety pts. underwent surgery and had complete reports. A complete resection was possible in 77% and 85% of operated pts. in arm A and arm B, respectively. The rate of complete histologic response was 2.5% after CTX and it reached 17% after CRTX (p=0.06). Despite increased postoperative mortality after chemoradiotherapy (5 vs. 2 pts.) the median survival time (32.8 mo) and the 3- year survival rate (43%) were improved in this patients group compared with patients of arm A (21.1 mo, 27%)(logrank p=0.14). Conclusions: This randomized study demonstrates that albeit its increased mortality preoperative chemoradiotherapy appears to prolong survival compared with preoperative chemotherapy in locally advanved esophago-gastric adenocarcinomas. Although accrual was below that planned, the observed difference in survival is clinically important and calls for further randomized trials in patients with this disease. No significant financial relationships to disclose.
Randomized phase II trial comparing folfirinox (5FU/leucovorin [LV], irinotecan [I] and oxaliplatin [O]) vs gemcitabine (G) as first-line treatment for metastatic pancreatic adenocarcinoma (MPA). First results of the ACCORD 11 trial
Authors: Ychou M. , Desseigne F. , Guimbaud R. , Ducreux M. , Bouché O. , Bécouarn Y. , Adenis A. , Montoto-Grillot C. , Luporsi E. , Conroy T. 
Published: March 2020

4516 Background: In a phase II trial of Folfirinox (F) in 35 MPA patients (pts), we reported a 26% response rate and median survival of 9.5 months (mo) with quality of life improvement (Conroy, JCO 2005). The aim of this phase II trial was to compare the response rate and safety of F vs G in pts with MPA. Methods: Chemotherapy-naïve pts aged 18–75 years with histologically or cytologically confirmed measurable MPA were randomized to receive G (1,000 mg/m2 IV weekly x 7 for 8 weeks [wks] then weekly x 3 out of 4 wks) or F (O 85mg/m2 d1 + I 180mg/m2 d1 + LV 400mg/m2 d1 followed by 5FU 400mg/m2 bolus d1 and 2,400 mg/m2 46h continuous infusion biweekly). Patients were stratified by centre, performance status (ECOG 0 versus 1), and primary tumor location (head vs other). Primary endpoint was response rate. Results: From 01/05 to 11/06, all planned 88 pts (44 per arm) were enrolled. Median age was 56 yrs [35–76]. Currently, safety data for 81 pts (41F/40G) and efficacy data for 65 pts (31F/34G) are available (17 too early). One pt was ineligible in arm F. Two pts, one in each arm, did not receive protocol therapy. Median number of wks on treatment was 18 (F) and 7 (G). No toxic death occurred. Main grade 3–4 toxicities (arm F vs G) were G3 neutropenia (32%/17.5), G4 neutropenia (19.5%/0), G3–4 thrombocytopenia (12%/0), G3 vomiting (17%/2.5), G3 transaminases (0%/15) and G3–4 fatigue (27%/15).Confirmed partial responses (PR) rates (F/G) were 38.7% (12/31) and 11.7 % (4/34) according to the investigators and median duration of response was 6,3 and 4,6 mo. PR and stable disease (SD) were documented for 21/31 evaluable pts in arm F and expert review confirmed 13 PR (41.9 %) and 6 SD (19.3%). Conclusions: Folfirinox induces a response rate > 30% with manageable toxicity in ECOG 0–1 pts with MPA. According to these interim results, this trial will continue as a phase III study. Updated results will be presented at the meeting. Supported by a PHRC 2004 grant from the French Ministry of Health. [Table: see text]
Postoperative adjuvant gemcitabine plus oxaliplatin (GemOx) chemotherapy followed by chemoradiation in patients with pancreatic carcinoma: A multicenter phase II study
Authors: Mornex F. , André T. , Louvet C. , Seitz J. , Ychou M. , Lledo G. , Touboul E. , Partensky C. , Balosso J. 
Published: March 2020

4520 Background: Gemcitabine (Gem) is an active drug in metastatic pancreatic cancer and a very good radiosensitizer. We evaluated the safety and potential activity of adjuvant GemOx chemotherapy followed by concurrent Gem and irradiation (RT) after curative resection of pancreatic cancer. Methods: Fifty four patients were enrolled from October 2002 to January 2005 in this trial with potentially curative resection of pathologically confirmed adenocarcinoma of the pancreas with negative resection margins (R0). Gem 1000 mg/m2 (100 min) on d1 then Ox 100 mg/m2 (120 min) on d2 were given (q2w for 6 cycles) followed 4 weeks after by Gem 100 mg/m2 (30 min) combined with RT 50 Gy (2Gy fraction) for 5 weeks in patients with no residual toxicity nor recurrence. Results: The treated population (at least 2 induction cycles) included 49 patients (91%). Characteristics at baseline: median age: 59.2 yrs; Karnofsky performance status =80: 96%; stage TX: 10%, T1: 8%, T2: 41%, T3:39%; T4: 2% (TNM classification, 5th edition); lymph node positive: 43%; median time from surgery to inclusion was 43 days. Forty six patients (85%) received the 6 planned induction cycles and 41 patients (76%) completed chemoradiation. The recurrence free 1-year survival rate is 71% (N=49); (95% CI 0.581–0 845). Forty one patients (98% of the irradiated population) received the total 50 Gy radiation dose. The most common Gr 3/4 toxicities during induction chemotherapy (N=51) were: neutropenia 18%, thrombocytopenia 14%; nausea, vomiting, diarrhea:16%, neurotoxicity (Gr 3 only) 4%. Acute Gr 3/4 toxicities during chemoradiation (N=42): neutropenia 19%, thrombocytopenia 7.0%, neurotoxicity (Gr 3 only) 7%. No toxic death occurred on treatment. Conclusions: GemOX in adjuvant followed by Gem + Radiotherapy have a manageable toxicity profile with a promising 71% 1 year RFS. Data of OS will be communicated during the meeting. No significant financial relationships to disclose.
A patterns-of-care study of post-progression treatment (Rx) among patients (pts) with advanced pancreas cancer (APC) after gemcitabine therapy on Cancer and Leukemia Group B (CALGB) study #80303
Authors: Schrag D. , Archer L. , Wang X. , Romanus D. , Mulcahy M. , Goldberg R. , Kindler H. 
Published: March 2020

4524 Background: Gemcitabine is the mainstay of Rx for pts with APC. Practice guidelines encourage participation in trials after disease progression. We evaluated Rx after APC progression for pts in CALGB 80303 a randomized trial of gemcitabine + bevacizumab (GB) or placebo (GP). Methods: Of the 552 pts who began GP or GB Rx, 457 had comprehensive medical record review. Of these 355 progressed on protocol Rx. We evaluated post-progression Rx for these 355 pts - the record review (RecR) group. We also phoned a subgroup of 126 pts to inquire about Rx delivered at sites other than the accruing center - the record review & interview group (RecR + I) to determine whether any Rx had been administered and the specific agents used. Results: ChemoRx after progression on gemcitabine was distinctly uncommon. Based on RecR 239/355=67.3% and on RecR + I, 70/126=55.6% of pts received no chemoRx after progression on the study Rx. These proportions did not vary based on Rx assignment. Worse ECOG performance status at baseline and older age were associated with lower likelihood of post progression Rx. Notably, 99/355=27.9% of pts died within 4 weeks of progression. Conclusions: After progression on a clinical trial of gemcitabine Rx, <half of pts receive 2nd line Rx and remarkably few (<2%) receive further experimental Rx. Given the lack of well established Rx options, there appear to be lost opportunities for participation in early phase clinical trials. Coordinated strategies for second line Rx options might increase the evidence base for this challenging malignancy. Patterns of Post-Progression ChemoRx after Progression on Gemcitabine ± Bevacizumab in APC. [Table: see text] [Table: see text]
ATTAX: Randomised phase II study evaluating weekly docetaxel-based chemotherapy combinations in advanced esophago- gastric cancer, final results of an AGITG trial
Authors: Tebbutt N. , Sourjina T. , Strickland A. , Van Hazel G. , Ganju V. , Gibbs D. , Gebski V. , Munro S. , Cummins M. 
Published: March 2020

4528 Background: Docetaxel (T), cisplatin (C) and 5FU(F) are active agents in esophago-gastric cancer. A recent phase III study evaluating 3-weekly TCF demonstrated a survival advantage over standard therapy, but TCF was associated with high rates of hematological toxicity (30% incidence of febrile neutropenia/neutropenic infection) as well as non-hematological side effects (Van Cutsem et al, J. Clin Oncol. 24 4991–4997 2006). Weekly docetaxel is associated with a lower incidence of hematological toxicity. This randomized phase II study aimed to test weekly docetaxel based combination chemotherapy regimens with the aim of maintaining the activity of such regimens but reducing toxicity. Methods: Eligibility included; histologically confirmed, metastatic esophageal or gastric (OG) carcinoma, measurable disease, PS0–2, adequate organ function, no prior treatment, informed consent. Patients (Pts) were randomized to receive weekly (w) T 30mg/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 (X)1,600 mg/m2/d d1–14 q3w. The primary endpoint is confirmed response rate (RR), with each arm analyzed independently. Simon’s 2-stage design was used, with 5/21 responses required in the first stage to allow continuation to 50 pts per arm. Results: Response rates in each arm satisfied the first stage, and complete accrual of 106 pts was completed in May 2006. Demographics, toxicity and response rates are shown in the table . With a median follow-up of 14.6 months, progression free and overall survival times are 5.9 m and 12.8 m, and 4.2m and 10.1 m for wTCF and wTX, respectively. Conclusions: wTCF and wTX have encouraging activity and a far more favorable toxicity profile than TCF administered 3-weekly. Weekly docetaxel-based combination regimens should be evaluated further in this disease. [Table: see text] [Table: see text]
A randomized trial of chemoradiotherapy versus surgery alone in patients with resectable esophageal cancer
Authors: Carstens H. , Albertsson M. , Friesland S. , Adell G. , Frykholm G. , Wagenius G. , Myrvold H. E. , Farago I. , Stockeld D. 
Published: March 2020

4530 Background: The aim of this study was to compare survival in a randomized phase III trial of chemoradiotherapy (CHRT) versus surgery alone for localized resectable oesophageal cancer. Methods: Between 2000 and 2004, 91 patients with oesophageal cancer were enrolled in a Scandinavian multicenter study. Patients with resectable oesophageal squamous cell carcinoma (50%) or adenocarcinoma (50%) were randomized to chemoradiotherapy (CHRT) or surgery alone. Chemotherapy (CHT) was given in 3 cycles with cisplatin 100 mg/m2, day 1 and 5-fluorouracil 750 mg/m2/24 hours, infusion day 1–5, every three weeks. After one induction chemotherapy course, radiotherapy including the primary tumour and defined locoregional lymph nodes, was given concomitant with the following CHT cycles, to a total dose of 64 Gy, in 32 fractions. Surgery was performed according to Ivor Lewis and lymph nodes resected with standard two-field technique. Results: At a median follow-up of 51.8 month’s 65 deaths are noted. In the chemoradiation group 50% of the patients accomplished therapy according to protocol, 40% were treated with modifications of the protocol and radical resection was performed 76% of the patients. Median survival was 12.8 months for chemoradiation and 15.8 months for the surgery group. There was no significant difference in 1-year survival 56% and 55% for CHRT and surgery, respectively. By two years, survival curves diverge and 2-years survival was 37% (CI 95%: 23–51%) for the CHRT group and 25% (CI 95%: 12–39%) for the surgery group. At four years, survival was 29% for CHRT versus 23% for surgery (CI 95% CHRT: 16–43%, CI 95% Surgery: 10–36%). Both treatments were well tolerated and no treatment related deaths were recorded in any of the treatment arms. Most deaths were due to tumor disease (66%) in both groups. Conclusions: No statistically significant differences between the treatment arms were seen and survival results are equal to earlier reported. Both treatment arms were well tolerated. No significant financial relationships to disclose.
A multicenter phase II study of gemcitabine and S-1 combination therapy (GS therapy) in patients with metastatic pancreatic cancer
Authors: Ueno H. , Okusaka T. , Furuse J. , Yamao K. , Funakoshi A. , Boku N. , Ohkawa S. , Makimoto A. , Sato T. 
Published: March 2020

4550 Background: As shown in our previous phase I study (Oncology 2005, 69:421–427), gemcitabine and S-1 combination therapy (GS therapy) appears to be feasible and effective against advanced pancreatic cancer. The present multicenter phase II study was conducted to confirm the efficacy and toxicity of GS therapy for metastatic pancreatic cancer. Methods: Patients with histologically or cytologically proven pancreatic adenocarcinoma with at least one measurable metastatic lesion were eligible for the study. Other eligibility criteria included: no previous treatment for pancreatic cancer except surgery, age =20 and =74 years, ECOG performance status of 0 or 1, and adequate organ function. Gemcitabine was given intravenously at a dose of 1,000 mg/m2 over 30 min on days 1 and 8, and S-1 was given orally at a dose of 40 mg/m2 twice daily from day 1 to day 14, repeated every 3 weeks. The objective response rate was assessed according to RECIST. Results: A total of 55 patients from 10 institutions were enrolled between October 2004 and July 2005. The efficacy and toxicity were analyzed in 54 patients who received at least one course of GS therapy. The median number of treatment courses was 7 (range, 1–24+). Although no complete response was seen, a partial response was achieved in 24 patients, resulting in an overall response rate of 44% (95% CI, 30.9–58.6%). Twenty-six patients (48%) had stable disease. The median progression-free survival was 5.9 months (95% CI, 4.1–6.9 months) and the median overall survival was 10.1 months (95% CI, 8.5–10.8 months) with a 1-year survival rate of 33%. The major grade 3–4 toxicities were neutropenia (80%), leucopenia (59%), thrombocytopenia (22%), anorexia (17%), rash (7%), nausea (6%) and fatigue (6%). Hematological toxicity was mostly transient and there was only one episode of infection with grade 3–4 neutropenia. No treatment-related deaths occurred during the study. Conclusions: GS therapy produced a high response rate and good survival associated with an acceptable toxicity profile in patients with metastatic pancreatic cancer. A randomized phase III trial to confirm the efficacy of GS therapy is planned. No significant financial relationships to disclose.
Phase II trial of bevacizumab, gemcitabine, oxaliplatin in patients with metastatic pancreatic adenocarcinoma
Authors: Kim G. P. , Oberg A. L. , Foster N. R. , Jaslowski A. , Flynn P. J. , Campbell D. , Hedrick E. , Gray L. , Grothey A. , Alberts S. 
Published: March 2020

4553 Background: The combinations of gemcitabine and oxaliplatin (GemOx) and bevacizumab and gemcitabine have activity in pancreatic cancer. Based on these observations, the NCCTG initiated a multicenter phase II study to evaluate the combination of an active cytotoxic doublet and a targeted agent to determine whether improvement in 6-month survival in previously untreated patients with metastatic pancreas cancer could be achieved. Methods: Treatment consists of gemcitabine 1000 mg/m2 IV over 100 minutes and bevacizumab 10 mg/kg IV given on day 1, 15; oxaliplatin 100 mg/m2 IV is given on day 2, 16, repeated every 28 days. Eligibility includes: no prior chemotherapy, ECOG PS 0–2, bili< 2x UNL, AST< 5x 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, severe adverse events (AEs), or patient refusal. Results: Eighty-two patients were enrolled from 7/05 to 2/06. Median age was 63 (range: 32 - 86). 24 of 82 (29%) evaluable pts had a maximum grade ≥ 4 AE (at least possibly related to treatment). Grade 4 events included (% of pts): neutropenia (7%), thrombosis (6%), thrombocytopenia (5%), pneumonitis (2%), ischemia-cerebral (1%), abdominal infection (1%), small intestine perforation (1%), and small bowel leak (1%). Three patients died from grade 5 events (1-gastric perforation, 1-cerebral ischemia, 1-multi-organ failure). 80 patients were evaluable for outcome assessment (excludes 2 ineligible cases). Median follow-up was 10.3 months (range: 6.3 - 14.7) in the 19 patients still alive. 6-month survival was 65.0% (95% CI: 53.5% - 75.3%). Median survival was 8.1 months (95% CI: 6.5 - 9.3) and median TTP was 5.7 months (95% CI: 4.4 - 6.4). The confirmed response rate was 11.3% (95% CI: 5.3 - 20.3%) with 1 complete and 8 partial responses. Conclusions: In this multi-centered, cooperative group study, promising efficacy with this three-drug combination was observed especially in regards to six- month and median survival. The observed adverse events are comparable to historical controls although caution should be exercised in light of the three grade 5 events. [Table: see text]