bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pooled safety and efficacy analysis of the FOLFOX4 regimen (bi-monthly oxaliplatin plus fluorouracil/leucovorin) in elderly compared to younger patients with colorectal cancer
Authors: Sargent D. J. , Goldberg R. M. , Bleiberg H. , De Gramont A. , Tournigand C. , Andre T. , Rothenberg M. L. , Tabah-Fisch I. M. 
Published: March 2020

3517 Background: The combination of oxaliplatin, fluorouracil, and leucovorin is effective in many patients with colon cancer treated in either the advanced or adjuvant disease setting. To better identify the risks & benefits of this regimen for elderly patients we compared safety & efficacy data for the FOLFOX4 regimen (oxaliplatin plus fluorouracil/leucovorin administered bimonthly) in patients over & under 70 years of age. Methods: We conducted a retrospective analysis of 3742 patients (614 aged ≥ 70) with colorectal cancer enrolled in four clinical trials using the same FOLFOX4 regimen as adjuvant therapy, or as first- or second-line therapy in advanced disease. Endpoints included grade ≥ 3 adverse events, response rate (RR) (in studies of advanced disease), progression (metastatic)/relapse free (adjuvant) survival (P/RFS), overall survival (OS), and dose intensity. Results: Age ≥ 70 was associated with slightly higher rates of neutropenia and thrombocytopenia but no other grade ≥ 3 adverse events (see table). There was no difference in 60-day mortality (1.1% vs 2.3%, p=0.20). We observed no significant difference in any measure of therapeutic impact of FOLFOX based on age, including P/RFS, OS, response rate, or dose intensity (see table). Conclusions: The FOLFOX4 regimen maintains its efficacy/safety ratio in elderly patients with colorectal cancer, and was administered per protocol at similar drug doses compared to the younger patients enrolled on these trials. Age alone should not be a factor limiting the use of FOLFOX4 provided patients are carefully evaluated and monitored. This analysis was supported by Sanofi-Aventis [Table: see text] [Table: see text]
A phase II study of celecoxib (C) with irinotecan (I), 5-fluorouracil (F), and leucovorin (L) in patients (pts) with advanced or metastatic colorectal cancer (CRC)
Authors: Sanborn R. E. , Lenz H. , Haller D. G. , Benson A. B. , Dragovich T. , Robles C. , McMahon M. , Li H. , Mori M. , Mattek N. , Blanke C. D. 
Published: March 2020

3588 Background: Expression of cyclooxygenase-2 (COX-2), present in most CRC, is associated with a worse prognosis. C, a selective COX-2 inhibitor, has inhibitory effects against CRC which appear at least additive with chemotherapy preclinically. A multi-institutional phase II trial was conducted to evaluate C plus standard IFL as first-line treatment for pts with incurable CRC. Methods: C 400mg po BID starting Day #1; I 125mg/m2 iv weekly starting Day #15; F 500mg/m2 iv bolus weekly starting Day #15; L 20mg/m2 iv weekly bolus starting Day #15. Patients received IFL for 4 weeks followed by a two-week rest. C was continued during the rest. Pts were treated until disease progression or unacceptable toxicity. Primary endpoint was response with planned sample size of 47 patients. Results: 47 pts were consented and treated. Evaluable pt characteristics: Male/female (no.) = 34/13; mean age = 59.7; ECOG PS 0/1/2 (no.) = 31/14/2; cancer stage locally-advanced/distant/unknown (no.) = 10/28/9. Due to concerns of risk of excess cardiovascular (CV) toxicity the protocol was amended halfway through enrollment to exclude pts with PS 2, and to require low-dose aspirin (ASA) for pts at high risk for CV events. Pre-and post-modification (mod) results are shown in the table . In general hematologic toxicity was moderate. Non-hematologic toxicity was mostly gastrointestinal, but 25% experienced cardiac or vascular toxicity (1 cardiac arrest, 1 MI, 1 CHF, 3 arrhythmias, 2 DVT, 2 CVA, 1 hyper- and 1 hypotension). All cardiac events occurred before modification of the protocol. There was 1 treatment-related death from cardiac arrest. Conclusions: C may be given safely with IFL chemotherapy, if pts are carefully selected. Addition of low-dose ASA may reduce cardiac toxicity. Post-mod TTP and survival for C plus IFL appear superior to historical results for IFL, but a phase III study would be required for confirmation. [Table: see text] [Table: see text]
Phase III randomized controlled trial of hypotonic intraperitoneal cisplatin combined with oral UFT/PSK for the adjuvant treatment of gastric cancer invading the serosa
Authors: Tsujitani S. , Saito H. , Tatebe S. , Ikeguchi M. 
Published: March 2020

4027 Background: Peritoneal seeding is the most common pattern of recurrence in patients with gastric cancer invading the serosa who underwent curative gastrectomy. We developed hypotonic intraperitoneal cisplatin for preventing peritoneal recurrence in experimental models. Hypotonic cisplatin had a significant tumorcidal effect in vitro and in vivo. Hypotonic intraperitoneal cisplatin was tolerable in phase I clinical study. Now, we investigated the efficacy of the treatment in a multicenter prospective randomized controlled trial. Methods: 134 pts treated with curative resection for gastric cancer invading the serosa were randomized during surgery to one of 2 treatment arms. As per protocol, eligibility was confirmed by pathology and treatment course in 108 pts as follows: A -Hypotonic intraperitoneal cisplatin (100mg/m2) during surgery and systemic UFT (300mg/day) + PSK (protein-bound polysaccharide, 3g/day) (n=54) and B-Systemic UFT + PSK (n=48). Cisplatin diluted in 1,000 ml of warmed distilled water was injected to the abdominal cavity before closure of the abdomen. Drains were closed for 1 hour after injection of cisplatin. Results: Median follow up was 6.8 years. Postoperative complication rate and side effects were 21.3% and 30.8% in A-arm and 22.4% and 24.0% in B-arm. Tolerance was good in both arms. Peritoneal recurrence rate was 26.9% in A-arm and 40.0% in B-arm (chi-square p=0.16). Overall survival at 5 years was 62.0% and 31.0% in pts with or without hypotonic intraperitoneal cisplatin (log-rank p=0.03). Conclusions: Combining hypotonic intraperitoneal cisplatin and systemic oral chemotherapy improves the efficacy of oral chemotherapy after curative surgery for gastric cancer invading the serosa. No significant financial relationships to disclose.
A phase I study of S-1 administration and a 24-h infusion of cisplatin plus paclitaxel in patients with advanced gastric cancer
Authors: Iwase H. , Shimada M. , Tsuzuki T. , Okeya M. , Kobayashi K. , Hibino Y. , Watanabe H. , Horiuchi Y. , Goto H. 
Published: March 2020

4074 Background: S-1 may have a major role in the treatment of gastric cancer as single agent or as a component of combination chemotherapy in Japan. We previously reported a multicentric phase II study of S-1 combined with a 24-h infusion of cisplatin in patients with advanced gastric cancer. This combination was active, safe and had the possibility of being combined with other anticancer drug. Combination chemotherapy with S-1 and cisplatin plus paclitaxel for advanced gastric cancer might yield a stronger antitumor effect. The objective of this study was to determine the dose-limiting toxicity (DLT), the maximum tolerated dose (MTD), the recommended dose (RD), and the preliminary antitumor activity of S-1 and cisplatin plus paclitaxel for advanced gastric cancer. Methods: Paclitaxel was administered on day 1. A fixed dose of S-1 (70 mg/m2/day) was orally administered for 14 consecutive days from day 1, and a 24-h infusion of a fixed dose of cisplatin (60 mg/m2) was administered on day 14 of every 28-day cycle. Four dose escalation levels of paclitaxcel were studied (120, 140, 160, and 180 mg/m2). The DLT was defined as any of the following: grade 3 neutropenia lasting more than 5 days, grade 4 hematological toxicity, grade 3 non-hematological toxicity, or treatment delay of greater than 2 weeks as a result of toxicity. Results: Twenty patients were enrolled. Hematological and non- hematological toxicity of over grade 2 was not observed at dose level 1 and 2. Three patients started at dose level 3. One developed grade 3 neutropenia for 5 days following by grade 2 neutropenia lasted more than 10 days. Five more patients were added at this level. The treatment was delayed over 2 weeks in 1 out of 8 patients. Three patients started at dose level 4. One developed grade 3 neutropenia and needed longer than 14 days to recover. Three patients added this level. In total, at dose level 4 the treatment was delayed over 2 weeks in 3 out of 6 patients as a result of neutropenia. We considered level 4 is the MTD and the RD of paclitaxcel was 160 mg/m2 (dose level 3). The overall response rate was 75%. Conclusions: Triple combination chemotherapy consisting of S-1, cisplatin, and paclitaxel showed a tolerable dose of adverse reactions and favorable antitumor activity for gastric cancer. No significant financial relationships to disclose.
Phase II study of neoadjuvant chemotherapy (NAC) with S-1 and cisplatin (CDDP) for patients (pts) with metastatic or locally unserectable gastric cancer (MGC)
Authors: Nashimoto A. , Yabusaki H. , Nakagawa S. 
Published: March 2020

4078 Background: To improve the poor prognosis of pts with MGC, we conducted a phase II study to evaluate the feasibility and efficacy of intensive NAC to enhance surgical respectability and survival. Methods: Eligible criteria included histologically proven metastatic or locally unserectable gastric adenocarcinoma and measurable or evaluable disease, PS 0–2 and sufficient organ functions. The primary endpoint was overall survival and the secondary endpoints were overall resonse rate (ORR) and toxicities. Since Oct. 2000, chemotherapy-naïve 120 pts with MGC have received S-1 (80 mg/m2 orally intake for 21 consecutive days) and CDDP (50 mg/m2 intravenous drip infusion on day 8) as NAC. Treatment was repeated every 5 weeks. The median administered courses were three (range: 1–7), and median follow up periods were 13.8 months. Results: The proportion of the duration as an outpatient- therapy was 86%. 77.5% of pts (93/120) went to surgical resection; 36 had distal gastrectomy and 57 had total gastrectomy. ORR was 62.5% (CR 1, PR 74), and 61.7%, 75.7%, 28.6% and 23.8% for primary lesion, metastatic lymph nodes, liver metastases and peritoneal metastasis, respectively. Toxicity (grade 3/4): neutropenia 7.5%, thrombocytopenia 6.7%, anemia 6.7%, anorexia 5.8%, nausea 2.5%; no treatment related death. Survival: median 23 months; 1 year 79%; 4 year 31% in all pts, and 42 months; 83%; 38% in pts with gastrectomy, respectively. In univariate analyses, overall survival (OS) was predicted by the responder, limited tumor location, H0, P0, but not by age, sex, histological type, gross type, T-factor, N-factor, or performance status. In multivariate analyses, H0, P0 and responder independently predicted OS. In pts with gastrectomy, H0, curative resection, PS0 and responder predicted OS. Conclusions: NAC with S-1 and CDDP was feasible and useful for pts with MGC and resulted in a promising survival rate. No significant financial relationships to disclose.
The utility of PET scanning in the management of squamous cell carcinoma of the anus
Authors: Nagle D. , Henry D. , Iagaru A. , Mastoris J. , Chmielewski L. , Rosenstock J. 
Published: March 2020

4152 Background: PET scanning is an established modality that is useful in the clinical management of squamous cell carcinoma (SCC) of the head and neck and esophagus. This study evaluates the usefulness of PET scans in the management of anal SCC. Methods: Prospective case series of all patients treated for SCC of the anus between 2002 and 2006 in a multi-disciplinary oncology practice group. All patients had staging studies at diagnosis of anal SCC that included CT scan of the chest/abdomen/pelvis and PET scan. All patients with palpable inguinal adenopathy or PET scans positive for inguinal adenopathy underwent fine needle aspiration (FNA) of inguinal nodes. All patients were evaluated by physical exam (PE) and biopsy (Bx), when appropriate, within 3 months of completing treatment. All patients who completed combined chemoradiation for anal SCC and had a post-treatment PET scan were included in this study. Results: 14 of 20 treated patients met criteria for this study. Sensitivity of pre-treatment PET scan was 100% for primary tumor. Extra-pelvic sites with PET SUV<4.0 were uniformly negative for tumor. 66% of inguinal nodes identified by PET scan were FNA positive for metastatic disease. Post-treatment, combined PE and Bx accurately predicted presence or absence of disease in 93%. Post-treatment scans were obtained a mean of 7.6 months after chemoradiation (range 1 to 42 months). In these patients, PET scan sensitivity = 50%, specificity = 72%, predictive value positive (PVP) = 50%, predictive value negative = 80%. 64% of scans were performed within 6 months of treatment; in these, PVP = 33% and PVN = 66%. Conclusions: PET scanning for anal SCC provides accurate staging of disease at presentation and may alter treatment planning by identifying inguinal node involvement not apparent on clinical examination. In this series, PET scan results did not change post-chemoradiation management in any case. Importantly, resolution of primary tumor defined by PET scan was accurate only 80% of the time. PE and Bx within 3 months of treatment were more accurate than PET scan in assessing disease. Post-treatment evaluation of anal SCC should continue to include careful PE, CT scan and Bx when appropriate. No significant financial relationships to disclose.
Single versus sequential high-dose chemotherapy (HDCT) in patients with relapsed or refractory germ-cell tumors (GCT)
Authors: Lorch A. , Rick O. , Hartmann J. T. , Kollmannsberger C. , Metzner B. , Schmidt-Wolf I. , Berdel W. E. , Schirren R. , Beyer J. , Bokemeyer C. 
Published: March 2020

4511 Background: Patients (pts) with relapsed or refractory GCT may be cured by HDCT. It is unknown whether single or sequential HDCT is superior. Methods: Between 11/99 and 11/04, 216 pts with relapsed or refractory GTC were treated in a prospective, randomized, multicenter phase III trial with either one cycle of cisplatin 100 mg/m2, etoposide 375 mg/m2 and ifosfamide 6 g/m2 (VIP) plus three cycles of high-dose carboplatin 1500 mg/m2 and etoposide 1500 mg/m2 (CE, arm A) or three cycles of VIP plus one cycle of high-dose carboplatin 2200 mg/m2, etoposide 1800 mg/m2 and cyclophosphamide 6400 mg/m2 (CEC, arm B) followed by reinfusion of autologous peripheral blood progenitor cells. Primary study endpoint was the event-free survival (EFS) one year after randomization. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and toxicities. An event was defined as any deviation from the planned treatment, relapse, progression or death from any cause. The planned study size was 230 pts to detect a difference of 15% with an alpha error of 5% and a power of 80%. Results: The study was stopped after recruitment of 216 pts due to excess treatment-related mortality in arm B: 111 pts were randomized in arm A and 105 pts in arm B. Due to non-GCT histologies at review 5/216 pts had to be excluded from further analysis. With a median follow-up of 36 months, 109/211 (52%) evaluable pts are still alive and 91/211 (43%) are progression-free. At one year EFS; PFS and OS are 40%, 55% and 80% in arm A as compared to 37%, 49% and 61% in arm B. Treatment-related deaths mainly due to sepsis and cardiac toxicity were less frequent in arm A (4/111 pts, 4%) as compared to arm B (15/105 pts, 14%) (p = 0.01). Severe non-hematologic organ toxicities were also less frequent in arm A. Conclusions: Treatment with sequential high-dose carboplatin and etoposide is at least as effective but less toxic than single HDCT with carboplatin, etoposide and cyclophosphamide. No significant financial relationships to disclose.
Predicting men at high risk for PSA failure after salvage radiotherapy for rising PSA following prostatectomy
Authors: MacDonald O. K. , D’Amico A. V. , Sadetsky N. , Shrieve D. C. , Bakst A. W. , Carroll P. R. 
Published: March 2020

4570 Background: Single and multi-institutional reports have published results indicating 5-year PSA response rates of 30 to 50% in men following salvage radiotherapy (RT) for rising PSA after radical prostatectomy (RP) depending upon the patient and disease factors. We analyzed a longitudinal observational database of men who received salvage RT following RP for their prostate cancer to evaluate for predictors of PSA failure despite salvage RT. Methods: Data from the Cancer of the Prostate Strategic Urologic Research Endeavor database (CaPSURE) identified 5,336 men with RP between 1989 and 2004; 200 underwent salvage RT ≥6 months after RP. PSA recurrence following salvage RT was defined as a PSA >0.2 ng/mL. A measure of the association between clinical and pathologic characteristics in men experiencing PSA failure following salvage RT was examined using a chi-square metric. Univariable and multivariable analyses of predictors for PSA recurrence using a Cox proportional hazard regression model were performed. Results: After a mean follow-up of 18 months (range 1 to 131 months), 121 (62%) men experienced PSA recurrence at a mean 13.7 months after salvage RT. Significant associations between time to PSA recurrence after salvage RT were found with the clinical risk group (p < .01), clinical T category (p < .01), race/ethnicity (p = .04), extraprostatic extension (p < .01), seminal vesicle invasion (p < .01), and pre-salvage RT PSA level (p < .01). The pre-salvage RT PSA level (p = .003) and seminal vesicle invasion (p = .02) remained significantly associated with time to PSA recurrence on multivariable analysis. Conclusions: The pre-salvage RT PSA level and the presence of seminal vesicle invasion were significantly associated with time to PSA recurrence following salvage RT within the CaPSURE database. Men with these risk factors are at increased risk for PSA recurrence despite salvage RT suggesting that these men would be ideal candidates for entry onto phase III studies comparing salvage RT plus systemic therapy with salvage RT alone at the time of post-operative PSA failure. [Table: see text]
Cancer-specific survival following radical prostatectomy or radiation therapy and short course hormonal therapy in men with localized, unfavorable-risk prostate cancer
Authors: Tsai H. K. , Chen M. , McLeod D. G. , Carroll P. R. , Richie J. P. , D’Amico A. V. 
Published: March 2020

4572 Background: We estimated prostate cancer-specific mortality (PCSM) rates following radical prostatectomy (RP) or external beam radiation therapy (RT) and 6 months of androgen suppression therapy (AST) in men with unfavorable-risk prostate cancer. Methods: Between 1981 and 2002, 3,240 men with intermediate- (T2b or Gleason score 7 or prostate-specific antigen (PSA) > 10 to 20 ng/mL) or high-risk (T2c or Gleason score 8 to 10 or PSA > 20 ng/mL) prostate cancer were treated with RP (n = 2,690) or RT+AST (n = 550) and comprised the study cohort. If PSA failure occurred, defined by a postoperative PSA level > 0.2 ng/mL and rising or by the ASTRO definition following RT+AST, then men received salvage RT or life-long AST, respectively. Life-long AST was initiated if PSA failure occurred after salvage RT. Imaging of the pelvis and skeleton was negative for metastases at the time of any salvage therapy. Gray’s formulation was used to compare the cumulative incidence estimates of PCSM and to calculate the adjusted hazard ratios (HR) and associated 95% confidence intervals for initial treatment and known prognostic factors. Results: After a median follow-up time for living patients of 4.5 and 4.2 years for the RP and RT+AST cohorts, respectively, there were no significant differences in the estimates of PCSM following RP or RT+AST in men with intermediate- (p = 0.44) or high-risk (p = 0.26) disease. As shown in the Table , after adjusting for PSA level, Gleason score, and T-category, initial therapy was not significantly associated with PCSM for men with intermediate- (HR: 1.2 [95% CI: 0.3, 4.3]; p = 0.78) or high-risk (HR: 1.2 [95% CI: 0.5, 2.8]; p = 0.62) disease. Conclusion: Men with localized, unfavorable-risk prostate cancer who receive RT and short course AST as initial therapy appear to have similar PCSM rates as men who undergo initial RP followed by salvage RT and life-long AST after first and second PSA failure, respectively. [Table: see text] No significant financial relationships to disclose.
Talactoferrin alfa may prolong progression-free survival in advanced renal carcinoma patients
Authors: Srinivas S. , Stadler W. M. , Bukowski R. , Figlin R. , Hayes T. , Yankee E. W. , Jonasch E. 
Published: March 2020

4600 Background: Talactoferrin alfa (formerly known as recombinant human lactoferrin, rhLF) is a novel immunomodulatory 80 kD protein with demonstrated oral anti-tumor properties in animal models, and promising early results in patients with advanced renal cell carcinoma (RCC) in Phase 1/2 trials. Methods: An open label Phase 2 study of Talactoferrin Oral Solution at 1.5 g talactoferrin alfa b.i.d. given up to a maximum of 4 cycles of 12 weeks on, 2 weeks off was conducted at 6 sites. Eligibility included predominantly clear cell histology, failure of at least one prior systemic therapy, tumor progression within the prior 9 months, a performance status of <2 (ECOG) and adequate organ function. The primary endpoints were the incidence of 14-week progression-free survival (PFS) and overall tumor response (by RECIST). The statistical plan specified an objective of 12.5% response rate or a progression-free survival rate of ≥40% at 14 weeks. Secondary endpoints included median PFS and median overall survival (OS). Results: Forty-four patients were enrolled. Eighteen patients (41%) were considered low risk and twenty-six (59%) considered intermediate risk based on the Memorial Sloan-Kettering Cancer Center (MSKCC) criteria. There were no talactoferrin-related Grade 3 or 4 adverse events or laboratory abnormalities. The most common related grade 1 or 2 adverse events were gastrointestinal symptoms. There was one unconfirmed tumor response and the 14-week PFS was 55%. The median PFS was 21 weeks (46 weeks and 9.4 weeks in the patients with low and intermediate risk prognostic factors, respectively). The median OS has not yet been reached. Conclusions: Talactoferrin alfa is well tolerated. The 14-week PFS met the pre-specified criteria for success (>40%). Due to the heterogeneity of tumor biology of RCC, any further evaluation of talactoferrin in this population should be in a larger randomized trial. [Table: see text]