bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized controlled trial comparing docetaxel (D)-cisplatin (P) combination with D alone in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC): JCOG0207
Authors: Tsukada H. , Yokoyama A. , Nishiwaki Y. , Shinkai T. , Harada M. , Ando M. , Shibata T. , Ohe Y. , Tamura T. , Saijo N. 
Published: March 2020

7629 Background: Platinum-based chemotherapy is currently recommended as the standard approach for pts with advanced NSCLC. However prospective clinical trials specifically designed for elderly pts demonstrating the P benefit are still lacking. Therefore, we conducted a phase III trial to determine whether the addition of P to single agent-chemotherapy for elderly NSCLC pts could improve survival. Methods: Eligibility criteria included; chemotherapy-naive; stage III/IV NSCLC; age=70 and PS 0–1. Pts were randomized to receive either DP or D with minimization method balancing site, age (=74/=75) and stage (III/IV), and both regimens were given every 4 weeks. DP comprised D (20 mg/m2) and P (25 mg/m2) iv on days 1, 8, 15. D comprised D (25 mg/m2) iv on the same schedule. Primary endpoint was overall survival (OS). The planned sample size was 115 pts in each arm to provide 80% power to detect 0.667 hazard ratio for DP to D in OS and 2.5% one-sided alpha. Results: Between Apr 2003 and Apr 2006, 126 pts were randomized (D/DP: 63/63). The second planned interim analysis was performed on 112 assessable pts (D/DP:56/56, median age 76, =74/=75: 39/61%, male/female: 77/23%, PS 0/1: 39/61%, III/IV: 30/70%). Maturity of information, defined proportion of interim events to the planned events, was 26% (=49/191). As the one-sided p-value(p=0.00515) of the stratified log-rank test by age and stage was not lower than the critical value for the interim analysis, the formal criterion for stopping the trial failed to meet. However the Data and Safety Monitoring Board recommended study termination and disclosure of the results based on the strong interaction (two-sided p=0.077, hazard ratios [95% C.I.] for =74/=75: 0.23 [0.09–0.62]/0.72 [0.35- 1.49]) that DP may be beneficial for subgroup of age between 70- 74. Major Grade 3–4 toxicities were (%D/DP): neutropenia 4.9/13.1, anemia 1.6/16.4, anorexia 8.3/24.2, infection 11.7/8.1, pneumonitis 1.7/1.6. TRD occurred in 1 pt in DP arm. Conclusions: The interpretation of study results is limited due to early stopping and resultant loss of statistical power. But these data indicated that =74 young elderly have no more need to evaluate tolerability and efficacy of P. No significant financial relationships to disclose.
Update of the NCI multiinstitutional phase II trial of romidepsin, FK228, for patients with cutaneous or peripheral T-cell lymphoma
Authors: Piekarz R. , Frye R. , Wright J. , Figg W. , Allen S. , Kirschbaum M. , Zain J. , Hutchins L. , Showe L. , Fojo T. , Bates S. E. 
Published: March 2020

8027 Background: The histone deacetylase inhibitors (HDIs) are a class of differentiating agents undergoing clinical testing. Like other HDIs, romidepsin (FK228) modulates expression of genes involved in cell cycle regulation and markers of differentiation in cancer cell lines, leading to induction of differentiation or apoptosis. Romidepsin has demonstrated clinical activity in patients with T-cell lymphoma. Methods: Patients with CTCL (42) or PTCL (36) were enrolled in the NCI multi-institutional trial and assigned to cohorts based on extent of prior therapy and pathology. Romidepsin is administered on days 1, 8, and 15 of a 28 d cycle with a starting dose of 14mg/m2. Responses for patients with PTCL are measured using Cheson criteria, and CTCL using RECIST criteria. Results: Cohort one, composed of 27 patients who had previously received no more than 2 prior cytotoxic regimens of chemotherapy, has completed enrollment. Responses observed include 3 patients with CR and 7 patients with partial responses, yielding an overall response rate of 37%. Of note, responses were observed independent of stage of disease. Among 18 patients with stage IV disease, 6 patients had a complete or partial response, including 3 patients with Sézary syndrome. When including patients with greater than 2 prior cytotoxic regimens, the overall response rate was 31%. A replicate arm has been opened with the goal of confirming the response rate observed in the first cohort. Response data have not been evaluated from this arm at this time. Responses observed in 36 patients with refractory or relapsed PTCL includes 3 patients with CR and 8 patients with partial responses, comprising an overall response rate of 30%. Responses were observed independent of prior therapy, with some patients having undergone prior stem-cell transplant. Molecular endpoint analysis was performed on peripheral mononuclear cells (PBMNCs) and tumor biopsies from treated patients evaluating histone acetylation and changes in gene expression. Conclusions: Romidepsin as a single agent appears to have significant single agent activity in patients with CTCL and PTCL. Combination therapy with romidepsin may increase efficacy and should be pursued. This protocol remains open to accrual. No significant financial relationships to disclose.
A phase I/II study of lenalidomide (Len) in combination with rituximab (R) in relapsed/refractory mantle cell lymphoma (MCL) with early evidence of efficacy
Authors: Wang M. , Fayad L. , Hagemeister F. , Neelapu S. , Bell N. , Byrne C. , Knight R. , Zeldis J. , Kwak L. , Romaguera J. 
Published: March 2020

8030 Background: MCL remains a therapeutic challenge. R targets CD20 antigen on MCL cells while Len may target the microenvironment of MCL cells and enhance the ADCC activity of R. To test this hypothesis, we initiated a single-center; open label, phase I/II study. We now report the completed phase I. Methods: Eligible patients (pts) had 1–4 lines of prior therapy including prior thalidomide or R, regardless of resistance. Each cycle of treatment consisted of Len given orally daily on days 1–21 of a 28-day cycle and R 375 mg/m2 by IV infusion weekly for 4 weeks. A standard 3+3 dose escalation was used to determine MTD with Len doses at 10 mg, 15 mg, 20 mg, and 25 mg. DLT was defined as grade (G) 3 or 4 non-hematologic or G4 hematologic toxicity during the first cycle. Results: The phase I portion completed enrollment with 15 pts (4 at 10 mg, 3 at 15 mg, 6 at 20 mg and 2 at 25 mg). Thirteen pts were evaluable. Median age was 73 (62–84); median prior lines of therapy were 3 (1–4); median cycles received to date were 2 (1–7). Two DLT's occurred at 25 mg. One pt had G3 hypercalcemia. The other had G4 neutropenic fever and died of sepsis (G5) during the first cycle. Three additional pts were therefore enrolled at 20 mg. Common non-hematologic toxic events included pruritis (21 G1–2), hypercalcemia (9 G1–2, 1 G3), fatigue (9 G1–2), constipation (8 G1), diarrhea (6 G1–2), fever (6 G1–2), myalgias (4 G1–2, 1 G3) and elevated LDH (4 G1–2, 1 G3). Hematologic events included neutropenia (20 G1–2, 4 G3), thrombocytopenia (6 G1–2, 2 G3) and anemia (6 G1). There were no responses at 10 mg or 15 mg. At 20 mg after 2 cycles, 5 out of 6 pts achieved responses including 1 CR, 1 PR, 3 minor responses (MRs) and only 1 pt progressed. The 1 pt with PR went on to achieve a CR after 6 cycles. The 3 pts with MRs had tumor reductions by 43%, 40% and 38% respectively. These 3 patients with MRs continue to receive Len and might later achieve PR or CR. Conclusions: The MTD for Len with R in relapsed/refractory MCL was 20 mg, orally daily on days 1–21 of a 28-day cycle. Responses observed at 20 mg are promising with a favorable toxicity profile and are being evaluated further in an ongoing phase II study. [Table: see text]
Schedule of bortezomib administration may be an important determinant of single-agent activity in patients with relapsed or refractory follicular (FL) lymphoma and mantle cell lymphoma (MCL)
Authors: O'Connor O. , Hamlin P. , Moskowitz C. , Straus D. , Noy A. , Wright J. , Neylon E. , MacGregor-Cortelli B. , Portlock C. , Zelenetz A. 
Published: March 2020

8051 Background: We previously demonstrated the significant activity of bortezomib for the treatment of FL and MCL. The activity in MCL has been confirmed in a multi-center study leading to the recent approval by the FDA. The demonstrated activity was observed on the twice weekly schedule. Recent data using bortezomib in combination with rituximab suggested that weekly bortezomib was less toxic and possibly equally as efficacious as twice weekly bortezomib. This study does not allow a determination of weekly single agent activity alone. We sought to evaluate the single agent activity of bortezomb in FL and MCL administered on a weekly schedule. Methods: Pts with FL and MCL were treated with bortezomib at a dose of 1.8 mg/m2 weekly for 4 of 6 consecutive weeks. To date, 20 pts (12 FL, 8 MCL) have been treated on this schedule, of which 18 are assessable for response. Two pts were inevaluable: 1 pt received steroids for bronchitis (MCL); and 1 pt (FL) with grade 2 diarrhea withdraw consent making her data inaccessible. Results: The range of cycles administered was 1 to 8, with a median of 2. The weekly dosing schedule was well tolerated with 1 pt. developing neuropathy (grade 3). Fourteen pts completed at least two cycles of therapy and underwent restaging. Two pts had a PR (both FL), 8 had SD (5 FL, 3 MCL) and 4 had POD (2 FL, 2 MCL). The other 4 evaluable patients are now being restaged. Conclusions: These data suggest weekly dosing with bortezomib may not be as effective as twice weekly. Typically, bortezomib administered on the twice weekly schedule has an ORR of 30% in MCL and 50% in FL. Additionally, the frequency of pts. experiencing POD appears to be less common on the twice weekly schedule. One difference in the schedules is the dose intensity and dose density. A cycle of twice weekly bortezomib administers 1.7 mg/m2/week, while a weekly schedule administers only 1.2 mg/m2/week, a 30% difference in dose intensity and a 100% difference in dose density (1.33 × per week vs. .67 × per week). What remains unclear from a pharmacologic perspective is the relative importance of high Cmax vs high AUC exposures, and their impact on both toxicity and efficacy. These data suggest that schedule is critical in the activity of bortezomib. No significant financial relationships to disclose.
A multicenter phase II study of erlotinib and bevacizumab in patients with metastatic melanoma
Authors: Wyman K. , Spigel D. , Puzanov I. , Hainsworth J. , Kelley M. , Krozely P. , Sturgeon D. , Sosman J. 
Published: March 2020

8539 Background: Erlotinib and bevacizumab have demonstrated activity in a number of malignancies by virtue of interrupting interdependent signaling pathways thought important in tumorigenesis. Melanoma may be an appropriate target based on its expression of EGFR and VEGF. We conducted a phase II multi-institutional trial evaluating erlotinib and bevacizumab in advanced melanoma patients. Methods: Eligibility included measurable disease, ECOG PS = 0–1, adequate organ function, no more than one prior therapy for metastatic disease, and CNS metastases were allowed if limited and controlled. Patients received oral erlotinib 150 mg/day and bevacizumab 10 mg/kg IV Q 2 weeks with tumor evaluation every 8 weeks. The primary outcomes were response rate (RR), response duration, and frequency of PFS >6 months. Secondary outcomes included overall survival, safety, and tolerability. A two-stage accrual design was employed ensuring that = 3/21 patients had PFS >6 months before additional patients were accrued. Results: As of Nov 2006, 29 patients with metastatic melanoma were enrolled. A total of 23 patients were evaluable for response. The majority was male 19/29 (65%) and had a median age = 62 yrs (range 35–78 years). Fifteen of the 29 had stage M1c disease (51.7%) and 18/29 (62.1%) had a PS = 1. Ten patients (34%) had prior adjuvant therapy and 6 patients (21%) prior therapy for metastatic disease. There were 2/23 (9%) partial responses lasting < 6 months and 5/23 (22%) had stable disease lasting > 6 months. The median progression free survival of evaluable patients was 96 days (95% CI: 50 - 142 days). A total of 25 grade III toxicities were observed with the most common being rash/pruritis (n=4), pain (n=4), fatigue (n=3), hypertension (n=2) and diarrhea (n=2). Two grade IV toxicities were observed (myocardial infarction and bowel perforation) both thought to be due to bevacizumab. Conclusion: The combination of erlotinib (150 mg/day) and bevacizumab (10 mg/kg) appears potentially active in patients with metastatic melanoma with largely tolerable toxicities. Accrual of a total of 41 patients will be completed shortly. [Table: see text]
A randomized phase II study of EMD 121974 in patients (pts) with metastatic melanoma (MM)
Authors: Kim K. B. , Diwan A. H. , Papadopoulos N. E. , Bedikian A. Y. , Camacho L. H. , Hwu P. , Johnson M. M. , Colevas A. D. , Prieto V. G. 
Published: March 2020

8548 Background: EMD 121974 is a selective antagonist of avβ3 integrin, which promotes the proliferation of tumor-associated endothelial cells and potentially the survival of melanoma cells expressing avβ3 integrin. We conducted a randomized phase II trial of cilengitide in pts with MM to evaluate the clinical efficacy at 2 different doses. Methods: Pts with stage IV or unresectable stage III non-choroidal melanoma who had no more than 1 prior systemic therapy were enrolled. Pts at least 18 years of age and with ECOG performance status of 0 to 2 were eligible. All pts underwent baseline tumor biopsy and were randomly assigned to either 500 mg or 2,000 mg intravenous (IV) EMD 121974 twice weekly, using the following stratification factors: 1) prior systemic treatment; 2) visceral metastases; 3) serum lactate dehydrogenase level; 4) tumor avβ3 overexpression, where overexpression is defined as > 25% of melanoma cells staining positive. The primary objective of this study was to determine the progression-free survival rate at 8 weeks. Results: Twenty-nine pts were enrolled, and 26 pts (14 at 500 mg; 12 at 2,000 mg dose) were treated. Patient characteristics for 500 mg and 2,000 mg arm, respectively, are as follows: median age, 57 and 61; percentage (% age) of male, 50% and 50%; % age of ECOG performance status of 0, 79% and 58%; % age of stage IV, 79% and 75%; % age of tumor avβ3 overexpression, 21% and 25%. Three of 26 pts were progression-free at 8 weeks (2 at 500 mg; 1 at 2,000 mg dose). One pt at 2,000 mg had a prolonged partial response after initial 28% enlargement of target lesions. There were no grade 3 or 4 adverse events (AEs) except one pt with grade 3 lymphopenia at 2,000 mg. Although both doses of EMD 121974 were well tolerated, the 2,000 mg was associated with higher incidences of grade 2 fatigue, arthralgia, lymphopenia, peripheral neuropathy, and GI AEs. Optional tumor biopsies were performed on day 8, and the correlative studies to examine the molecular changes in the tumor are currently in progress. Conclusions: IV EMD 121974, 500 or 2,000 mg twice weekly, was well tolerated but had minimal clinical efficacy as a single-agent for MM. Supported by NCI grant N01 CM-17003 and CA16672 No significant financial relationships to disclose.
Capecitabine (Cap) and oxaliplatin (Ox) in elderly and/or frail patients with metastatic colorectal cancer: The FOCUS2 trial
Authors: Seymour M. T. , Maughan T. S. , Wasan H. S. , Brewster A. E. , Shepherd S. F. , O'Mahoney M. S. , May B. R. , Thompson L. C. , Meade A. M. , Langley R. E. 
Published: March 2020

9030 Background: Elderly/frail patients, though commonly treated, are under-represented in clinical trials. Evidence is needed to guide choices of drugs and doses in this population. Methods: FOCUS2 is a multicenter, 2x2 factorial randomized trial for patients with unpretreated metastatic colorectal cancer judged unfit for full-dose combination chemotherapy. After comprehensive health assessment (CHA), randomization was to: (A) simplified LV5FU2 infusional fluorouracil/leucovorin (FU); (B) OxFU; (C) Cap; or (D) OxCap. In each case, starting doses were 80% standard, with an option to escalate to full-dose at 6 weeks (wk). The factorial questions were: (A+B v C+D) - does replacing FU with Cap improve quality of life (QL)? (primary endpoint: improved global QL at 12 wk [QLQ-C30]); and (A+C v B+D) - how much does Ox improve efficacy in this population? (primary endpoint: progression-free survival (PFS). Results: 460 patients were randomized, 22% < 70 yrs; 35% 70–75 yrs; 43% > 75 yrs. 22% were performance status (PS) 0; 49% PS1; 29% PS2. Primary comparisons: (see table ): global QL did not favor Cap over FU. Comparison of PFS favored the addition of oxaliplatin but did not reach significance (HR 0.87, 95% CI 0.71–1.06, p=0.16). Secondary comparisons: Compared with FU, Cap did not affect RR, PFS or 60-day mortality, but it increased the risk of gr =3 toxicity. Oxaliplatin significantly improved RECIST response (RR) by wk 12, did not increase gr =3 toxicity or 60-day mortality, but reduced the chance of improved QL at 12 wk. Conclusion: In this frail elderly population, substituting Cap for FU did not improve overall QL or efficacy, and significantly increased toxicity. Addition of Ox gave significantly higher anticancer activity without increasing toxicity, but at the cost of some reduction in QL at 12 wk. Planned analyses include correlating baseline CHA with treatment outcome. [Table: see text] [Table: see text]
Osteopenia and osteoporosis in untreated non-Hodgkin's lymphoma patients: An important and potentially treatable survivorship issue in lymphoma
Authors: Thompson M. A. , Huen A. , Toth B. B. , Vassilopoulou-Sellin R. , Hoff A. O. , Murphy W. A. , Sanjoro H. , Bekele B. N. , Arbuckle R. B. , Hagemeister F. B. 
Published: March 2020

9055 Background: Alkylating agents and steroids can cause premature osteoporosis, increasing the risk of vertebral and hip fracture. The bisphosphonate pamidronate every 3 months can reduce bone loss and the risk of new vertebral fractures in lymphoma patients receiving chemotherapy.(Kim et al., 2004 Am J Med) We are conducting a randomized study of the more potent bisphosphonate zoledronic acid in untreated non-Hodgkin's lymphoma (NHL) patients to study chemotherapy induced bone loss. Methods: During the accrual period, we report the baseline bone mineral density (BMD) characteristics for screened untreated NHL patients. Exclusion criteria included bone fractures, BMD T-scores worse than -2.0, CrCl < 60 mL/min, dental problems, prior bisphosphonate or significant steroid use. Patients accrued to the study were randomized to receive either: 1) oral calcium and vitamin D (Ca+D) or 2) Ca+D and 4 mg zoledronic acid IV at baseline and at 6 months. Results: Patient characteristics: 59 males and 55 females with median age 63 (range: 18–87). Lymphoma types: B-cell n=111, T-cell 3; follicular (FL) 56, diffuse large B-cell (DLBCL) 33, mantle cell 8, and others, totaling 114 patients. Of untreated NHL individuals screened for baseline BMD to date 11/114 (10%) had osteoporosis and 62/114 (54%) had osteopenia or osteoporosis. The lowest BMD was a T-score of -4.4. Other bone, dental, and endocrine abnormalities excluded some patients from treatment randomization. Patients with T scores < -2.0 were considered for off-study treatment with bisphosphonates. Osteopenia and osteoporosis were common across lymphoma subtypes: FL 25/56 (45%), DLBCL 20/33 (61%), mantle cell 6/8 (75%), and marginal zone 5/6 (83%). The low rate of osteopenia/osteoporosis of 25% for Burkitt/Burkitt-like lymphoma may reflect fast lymphoma kinetics without associated increase in bone loss. Conclusions: Baseline testing of BMD revealed osteopenia or osteoporosis in the majority of untreated NHL patients. This widely available and non-invasive test should be considered in untreated NHL patients. Our ongoing clinical trial will address the potential role of zoledronic acid in preserving bone density for survivors of NHL. ClinicalTrials.gov Identifier: NCT00352846 [Table: see text]
A randomized, double-blinded, pilot trial of aprepitant added to standard antiemetics during conditioning therapy for hematopoietic stem cell transplant (HSCT)
Authors: Bubalo J. S. , Leis J. F. , Curtin P. T. , Maziarz R. T. , Kovascovics T. J. , Meyers G. , McCune J. S. , Munar M. Y. , Hayes-Lattin B. , Jones N. 
Published: March 2020

9112 Background: Antiemetic prophylaxis for standard dose chemotherapy has improved while that for high dose chemotherapy ± total body irradiation (TBI) has not. Aprepitant (A), a neurokinin-1 antagonist, was added to standard antiemetic therapy for planned conventional HSCT to test for improved emesis control. Methods: During cyclophosphamide (Cy)-based conditioning therapy patients were randomized to receive ondansetron (O) ± dexamethasone plus A or a placebo (P) on days of chemo/radiotherapy. The primary aim was to reduce N/V during and after HSCT conditioning. Nausea, emesis, and nutritional intake were evaluated from the onset of therapy through day +7. Busulfan doses were targeted to disease appropriate AUCs and pharmacokinetic (PK) analysis was performed on Cy, Cy- metabolites (HCY & CEPM), and A. Responses were defined as Complete (CR) - no emesis, mild-moderate nausea, and Major (MR) - 1–2 emesis on only 1 day with any level nausea or no emesis with severe nausea. Results: Fifteen patients have been randomized per arm. Eleven patients received TBI (1,200 cGy) CY (120 mg/kg) and 19 received Bu (16 mg/kg) CY (120 mg/kg). A/P was begun on Day -7 (125 mg) with the first O dose and given daily (80 mg) through day +4 (alone on days +1 through +4). Overall responses (CR + MR) were seen in 14/15 A patients and 7/15 P patients. (p=0.014) No emesis occurred in 10/15 A patients and 5/15 P patients (p=0.143). Preliminary PK show the observed AUCs of CY, HCY and CEPM, for both regimens and PK differences between the 2 regimens, were consistent with previously published data. Most busulfan patients, 87%, required dose adjustments (primarily reductions) to stay within target AUCs. Anti-seizure prophylaxis with phenytoin may significantly decrease A levels, but this didn't appear to be clinically relevant. Adverse effects were similar between arms. One case of sinusoidal obstruction syndrome occurred in the P arm. Conclusions: In this interim analysis, aprepitant added to standard antiemetics improved emesis prevention during Cy-containing conditioning therapy prior to HSCT, without significant changes in Cy pharmacokinetics or increased toxicity. Data on the target accrual of 40 patients will be presented. [Table: see text]