tbuckley/cabot-search huggingface dataset:
Phase I study of s-1 plus fractional cisplatin as adjuvant chemotherapy for advanced gastric cancer in an outpatient setting (KOGC-03).
Authors: Taiki Ono, Tsunehiro Takahashi, Rieko Nakamura, Norihito Wada, Hirofumi Kawakubo, Hiroya Takeuchi, Yoshiro Saikawa, Tai Omori, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2015)

157 Background: The aim of this phase I study is to confirm the dose of cisplatin as adjuvant combination chemotherapy with S-1 in gastric cancer patients in an outpatient setting. Methods: The first course was initiated with S-1 monotherapy on days 1-28. From the second to sixth course, S-1 was administered on days 1-28 and cisplatin was added on days 1, 15, and 29. Dose level of cisplatin was escalated as follows: 20 mg/m2 (level 1); 25 mg/m2 (level 2); 30 mg/m2 (level 3). Results: Between Sep. 2010 and Feb. 2014, 13 patients were entered into this study. The median age was 65 years. All patients had a performance status of 0. Final stages were: Stage IIIA, 4; Stage IIIB, 8; and Stage IIIC, 1. The first three patients enrolled at level 1 and none of the three patients experienced Dose-limiting toxicity (DLT). However, one patient at level 2 could not complete administration of cisplatin. Therefore, an additional three patients were entered into level 2. Since these patients did not experience any severe adverse events, level 2 was completed. The first patient enrolled at level 3 had experienced leukocytopenia and elevated bilirubin. These toxicities did not resolve to the level of the starting criteria for the next course within 21 days. In the next patient, the third course could not be started within 21 days because of fatigue and anorexia. Based on these results, the Maximum Tolerated Dose and Recommended Dose were confirmed as level 3 and level 2, respectively. The DLT was &gt;21-day delay of starting the next course. Three patients at level 1 completed combination adjuvant chemotherapy between the second and sixth course based on the protocol. During these treatments, no grade &gt;2 hematological or non-hematological toxicities were experienced. At level 2, two out of six patients completed 5 courses of combination chemotherapy without experiencing severe adverse events. Three out of six patients at level 2 had received 4 courses of combination chemotherapy. Conclusions: Although further clinical trials are recommended to evaluate efficacy, this combination S-1 plus cisplatin regimen is expected to become a standard adjuvant treatment for gastric cancer in the outpatient setting. Clinical trial information: 601995.
At-home management of aplastic phase following high-dose melphalan with stem cell rescue for multiple myeloma patients.
Authors: M. V. Martino, R. Fedele, G. Console, E. Massara, L. Russo, T. Moscato, G. Messina, S. Al Sayyad, G. Pellicanò, G. Irrera
Journal: Journal of Clinical Oncology (2011)

e18577 Background: After high-dose chemotherapy with autologous stem-cell support, long hospital stays in the aplastic phase are expensive, lead to increased risk of hospital infections and to increasing pressure on available hospital beds. Methods: We developed a home care regimen that allows patients to be at home for the aplastic period, without daily hospital visits. Between June 2010 and December 2010, transfer of supportive care to the home setting took place was proposed for 20 patients with multiple myeloma and treated with melphalan 200 mg/mq and autologous stem-cell transplant. 12 patients refused and 8 have accepted the program, respectively. Results: In the inpatient cohort, the supportive care designed for at home use was administered in the hospital until neutrophile recovery to 0.5 x 109/l. In the second, home care cohort consisted of patients who were discharged the day after stem cell reinfusion, after which specialized home care nurses delivered all supportive care including transfusions and parenteral antibiotics at home, with double day check-up in home by the transplant physician. Inpatients were hospitalized in the aplastic phase for a median of 14 days. Patients in the home care cohort were at home in the aplastic phase for a median of 12 days. No readmissions in hospital related to side effects was observed in home care cohorts. No infectious deaths or unexpected emergencies occurred in the home care cohort. Neither was there any suggestion of an increased number of fevers, infections, or other complications. Conclusions: At home management in the aplastic phase after high-dose melphalan and stem cell transplant by community-based professionals is feasible without signs of increased toxicity or infections.
PrEP for key populations in combination HIV prevention in Nairobi: a mathematical modelling study
Authors: Ide Cremin, Lyle McKinnon, Joshua Kimani, Peter Cherutich, Gloria Gakii, Festus Muriuki, Katharine Kripke, Robert Hecht, Michael Kiragu, Jennifer Smith, Wes Hinsley, Lawrence Gelmon, Timothy B Hallett
Journal: The Lancet HIV (2017)
Response to the first-line FOLFOX plus bevacizumab (BEV) therapy to predict responses to the subsequent therapies and survival in the BEV beyond progression (BBP) strategy for metastatic colorectal cancer: A retrospective analysis of CCOG-0801 study.
Authors: Goro Nakayama, Keisuke Uehara, Naomi Hayashi, Chie Tanaka, Daisuke Kobayashi, Mitsuro Kanda, Suguru Yamada, Tsutomu Fujii, Hiroyuki Sugimoto, Masahiko Koike, Shuji Nomoto, Michitaka Fujiwara, Yuichi Ando, Yasuhiro Kodera
Journal: Journal of Clinical Oncology (2014)

428 Background: The aim of this study was to evaluate the association of early tumor response to the first-line bevacizumab (BEV) combination therapy with efficacy of the subsequent therapies and survival during the BEV beyond progression (BBP) strategy for metastatic colorectal cancer (mCRC) patients. Methods: We analyzed a pooled data set from the previous phase II studies of mCRC, testing BBP strategy with the first-line mFOLFOX plus BEV (N=47) and the second-line FOLFIRI plus BEV (N=31). Patients were classified into either responders (R group, n=29) with tumor shrinkage (complete response [CR] + partial response [PR]), sub-responders (SR group, n=11) with stable disease (SD) and non-responders (NR group, n=5) with disease progression (PD) at the point of initial three months of the first-line therapy. The tumor response and PFS in the subsequent therapies and OS were evaluated. Results: In the first-line FOLFOX+BEV therapy, further tumor shrinkage was not achieved after the initial three months. PFS was 15.0 months for the R group, 8.9 months for the SR group and 2.9 months for the NR group, respectively, and there was statistical significance favoring the R group (p=0.001). In the second-line FOLFIRI+BEV, RR and DCR were 39 and 78% in the R group, 14 and 57% in the SR group, and 0 and 0% in the NR group, respectively. No additional response to the first-line therapy was observed in all groups, except for only one patient in the SR group. PFS was 8.8 months for the R group, 6.0 months for SR group and 1.4 months for NR group, respectively, and the R group was significant predictor for prolonged PFS in the second-line setting. OS were 30.8 months for the R group, 24.7 months for the SR group, and 11.1 months for the NR group, respectively. Early disease control (R+SR) was significant predictor for OS (hazard ratio [HR]: 8.48, p&lt;0.01) in multivariate analysis. Conclusions: These findings indicate that the tumor response within initial three months of first-line BEV combination chemotherapy could predict efficacies of subsequent treatments and OS in the BBP strategy for mCRC patients. Clinical trial information: UMIN000006818.
EORTC trial 22991: Results of a phase III study comparing 6 months of androgen suppression and irradiation versus irradiation alone for localized T1b-cT2aN0M0 prostate cancer.
Authors: Michel Bolla, Alphonsus C.M. Van Den Bergh, Christian Carrie, Salvador Villà, Petros Kitsios, Philip M. Poortmans, Santhanam Sundar, Elzbieta M. van der Steen-Banasik, John Armstrong, Jean-Francois Bosset, Fernanda Herrera, Bradley Pieters, Annerie Slot, Amit Bahl, Laurence Collette, Philippe Maingon
Journal: Journal of Clinical Oncology (2016)

22 Background: Up to 30% patients irradiated for intermediate- or high-risk localized prostate cancer experience relapse biochemically within 5 years. We assessed if biochemical disease-free survival (BDFS) is improved by adding 6 months of androgen suppression (AS) – twice 3-month depot LHRH-agonist to primary irradiation (RT) for intermediate or high risk localized T1b-cT2a N0M0 prostate cancer. Methods: 819 patients staged cT1b-c with PSA ≥ 10 ng/ml or Gleason ≥ 7 or cT2a (UICC TNM 1997) N0 M0 with PSA ≤ 50 ng/ml were randomized between RT or RT+ADT. Centers elected one dose of prostate irradiation: 70, 74, or 78 Gy. Irradiation of pelvic nodes was left to the discretion of each institution. The trial aimed to show an increase of +7.5% in 5-year BPFS (HR=0.714) with 80% power. This requires 274 events in intent-to-treat analysis. HRQoL was assessed by EORTC QLQ-C30+PR25 (ClinicalTrials.gov NCT00021450). Results: Patients were 70 y old in median, 88% had WHO PS 0, 74.8% were intermediate risk, and 24.8% high risk. In the RT arm, 407/409 received RT, in the RT+ADT, 403/410 received RT+ AS and 3 RT. Six patients refused treatment. After a median follow-up of 7.2 years, 201 and 118 events for BPFS were observed in the RT and RT+ AS arm. RT+ AS improved BPFS compared to RT (HR=0.53, CI: 0.42-0.67, P&lt;0.001) irrespective of the radiation dose (heterogeneity P&gt;0.1). The 5-y BPFS increased from 69.3% to 82.5%. Clinical PFS was also statistically significantly improved (205 events, HR=0.63, CI: 0.48-0.84, P=0.001, +7.9% at 5 years). Late genitourinary toxicity was reported by 5.9% vs. 3.6% of the patients, on RT+ AS and RT, respectively (p=0.14), whereas 27.0% vs 19.4% reported severe impairment of sexual function (p=0.010). Overall HRQoL did not differ between the groups. Hormonal treatment symptoms, sexual activity and functioning scales are clinically significantly impaired by AS at month 6 and year 1; from year 2 no marked difference is seen. Conclusions: The addition of 6 months of medical castration to primary irradiation improves BPFS and PFS in intermediate- and high-risk localized T1b-cT2a N0M0 prostatic carcinoma with no persistent detriment on HRQoL or sexual function. Clinical trial information: NCT00021450.
Increased progression-free and overall survival in patients with breast cancer with menopausal symptoms or arthralgia/myalgia during adjuvant treatment with exemestane or tamoxifen: Results of the German TEAM trial.
Authors: D. G. Kieback, P. Hadji, T. Menschik, A. Hasenburg, J. Tams, M. Ziller
Journal: Journal of Clinical Oncology (2011)

523 Background: Previous studies have suggested a correlation between the occurrence of vasomotor or joint symptoms during tamoxifen or aromatase inhibitor treatment and improved clinical response. We assessed if there was any correlation between treatment-emergent adverse events during exemestane or tamoxifen treatment and clinical response. Methods: A retrospective analysis of the German cohort of the TEAM trial was performed to assess progression-free survival and overall survival in patients with and without menopausal symptoms or arthralgia/myalgia during adjuvant treatment with exemestane or tamoxifen. Results: A total of 1,502 patients were included in this analysis; 739 patients received tamoxifen and 763 received exemestane. Patients reporting menopausal symptoms and patients reporting arthralgia/myalgia during tamoxifen or exemestane treatment had significantly longer overall survival and progression-free survival. The effect on overall survival was irrespective of treatment. Progression-free survival was significantly improved in exemestane-treated patients reporting menopausal symptoms or those reporting arthralgia/myalgia versus those not reporting these adverse events. There was no significant difference in progression-free survival between tamoxifen-treated patients reporting these symptoms versus those who did not. A combined analysis of patients reporting either menopausal symptoms or arthralgia/myalgia showed that overall survival and progression-free survival was significantly improved in patients reporting one of these symptoms versus those not reporting either symptom. In this analysis, the effect on overall survival and progression-free survival was irrespective of treatment. Conclusions:Our results suggest that the occurrence of menopausal symptoms or arthralgia/myalgia during treatment with tamoxifen or exemestane is associated with significantly improved overall survival.
Patient, family member, and clinician perspectives on advance care planning (ACP) in hematology and hematopoietic stem cell transplantation (HSCT).
Authors: Reanne Booker, Jessica Simon, Shelley Raffin Bouchal
Journal: Journal of Clinical Oncology (2016)

7 Background: Studies have found that ACP engagement remains low in patients undergoing HSCT in spite of the high risks of treatment-related morbidity and mortality. Methods: This qualitative study used Thorne’s Interpretive Description methodology. Participants were accrued from hematological malignancy outpatient clinics at a tertiary oncology center and underwent audio-recorded semi-structured interviews. Analysis involved meticulous review of interview transcripts. The constant comparative method was utilized; data collection occurred concurrently with analysis until saturation of themes was achieved. Results: The study involved 6 patients, 5 family members and 8 clinicians (physicians, nurses, social worker). Participants thought that ACP was both acceptable and important yet many had not engaged in ACP. Perceived barriers to ACP included: system-related barriers such as lack of process for ACP, lack of time and/or resources; patient-related factors such as lack of understanding of disease, prognosis and/or expectations of HSCT, lack of patient/family understanding of ACP, a desire to ‘focus on positives’; and disease/treatment-related factors such as unpredictability of the disease and treatment trajectories in hematology and HSCT. Potential facilitators identified by participants included: integrating ACP as part of routine HSCT care, involving the multidisciplinary team in ACP, and introducing ACP early and revisiting frequently. Conclusions: This study revealed various barriers and facilitators related to participation in ACP. We are using the results of this study to inform and tailor interventions on ACP at our center. Introducing ACP as part of standard care in HSCT and providing ongoing facilitation of ACP, including discussion of disease and treatment expectations at the outset, and when complications arise, may assist patients and families in recognizing how ACP fits into their care. Given the inherent unpredictability in this population, we suggest revisiting ACP frequently to optimize patient experience and ensure patients and family members are aware of other treatment options including supportive and palliative care.
A phase II clinical and PET study of erlotinib and bexarotene for heavily pretreated advanced non-small cell lung cancer (NSCLC)
Authors: K. H. Dragnev, J. R. Rigas, M. Seltzer, W. DiSalvo, S. Simeone, D. Johnstone, W. Nugent, E. Dmitrovsky
Journal: Journal of Clinical Oncology (2008)

19079 Background: We previously reported a phase I trial of the EGFR tyrosine kinase inhibitor, erlotinib (E), and the nonclassical retinoid, bexarotene (B), in patients (pts) with advanced aerodigestive tract cancers showing minimal toxicities and preliminary evidence of clinical activity. Combining E with B also induced at least additive suppression of growth and cyclin D1 expression in human bronchial epithelial cells and in some lung cancer cell lines. Methods: A phase II trial of E and B was conducted in pts with stage IV NSCLC, mostly as third line or higher. Primary objective - radiographic response rate. Secondary objectives - survival, time to progression, toxicities, and correlation of early metabolic response by PET at 8–12 days and 2 months. Doses: E 150 mg, B 400 mg/m2 daily orally. Results: Forty pts were enrolled including 52% women and 60% with adenocarcinoma. Median age was 66 years, median number of prior therapies was 2 (range 0–5), 12% were current smokers, 17% were never smokers. Nine pts had prior anti-EGFR therapy. Six pts withdrew consent, mostly within the first month for difficulty swallowing pills. Toxicities were mild with frequent hypertriglyceridemia and skin rash. Treatment was discontinued for grade 3 pulmonary hemorrhage (1), rash/mouth sores (1), cough (1), hypereosinophilic syndrome (1), and abdominal pain (1). There were 2 objective partial responses, 7 pts had stable disease including one pt with prior gefitinib (35 wks). Median time to progression was 7 wks, median overall survival was 21 wks (intent-to-treat). Analysis of metabolic activity on early PET imaging at 10 days and the radiographic findings at 2 months will be presented. A proof-of-principle pilot study will assess if this combined regimen is better than the single agents in repressing EGFR and/or cyclin D1. Conclusions: The regimen of E and B is well tolerated and shows evidence of activity in heavily pretreated patients with NSCLC. Taken together, these findings implicate clinical benefit of dual targeting of EGFR and cyclin D1 in NSCLC. A randomized trial comparing E+B to E is needed to confirm the enhanced activity of the combination. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech, OSI Eisai, Genentech, Ligand
Quality of life findings from a multicenter, multinational, observational study of patients with metatstatic hormone-refractory prostate cancer
Authors: M. Fishman, P. Jacobsen, P. Mulani
Journal: Journal of Clinical Oncology (2005)

8106 Background: Although Quality of Life (QoL) is often reported in randomized clinical trials, few data exist outside the setting of investigational treatment intervention. A multinational observational study of patients with metastatic hormone-refractory prostate cancer (M+HRPC) was conducted to study QoL as assayed by different instruments and to study resource utilization and clinical practices. This abstract focuses on the QoL aspect of this study. Methods: 280 patients were enrolled in the US, Canada (North America, n = 99), the UK, France, Germany, Italy (Europe, n = 141), and Australia (n = 40). QoL data were collected using Functional Assessment of Cancer Therapy-Prostate (FACT-P), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C-30) and Euro-Qol (EQ-5D) surveys at baseline and at months 3, 6, and 9. Mean change from baseline to final visit was computed for each domain, and statistical testing was conducted using paired t-tests (baseline vs final). A trend test using mixed models was conducted to determine if the slope of change of QoL over time was different from zero. Results: The table below lists baseline mean, final visit mean, mean change results, and trend test parameter estimates for the QoL domains. With the exception of the EORTC Pain Domain, higher scores indicate better QoL. P <0.001 for each mean change and trend test result. Conclusions: Patients experienced a statistically significant and rapid decline in QoL. These data quantify the deterioration of QoL and illustrate the opportunity and need for palliative therapy in patients with M+HRPC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories Abbott Laboratories Abbott Laboratories, Chiron
Study of oral clofarabine plus low-dose cytarabine in previously treated AML and high-risk MDS patients at least age 60.
Authors: K. M. Smith, E. Estey, J. M. Pagel
Journal: Journal of Clinical Oncology (2011)

6549 Background: Given the lack of good treatment options for older patients with AML and high-risk MDS, it is imperative that new regimens that are well-tolerated and effective be created. The combination of IV clofarabine and cytarabine has been shown to be well tolerated and have efficacy in early phase studies in older patients with AML. In a prospective randomized phase II study, older patients with newly diagnosed AML were treated with clofarabine 30 mg/m2 IV daily for 5 days with or without low dose cytarabine (LDAC) 20 mg/m2 SC daily for 14 days. Thirty-one percent of patients receiving clofarabine alone had a complete remission (CR) compared to 63% of patients receiving clofarabine with LDAC (Blood 2008). Use of oral, rather than IV, clofarabine offers obvious advantages to older patients. In a single-arm, open-label, phase II clinical trial, patients with higher-risk MDS were given oral clofarabine at 20-40 mg/m2 for 5 days every 4-8 weeks for up to 12 cycles. The response rate was 43% with a CR rate of 25% (JCO 2010). Methods: This is a single-arm, open-label, phase I/II study of oral clofarabine plus LDAC. The clofarabine will be administered daily for 5 days combined with LDAC at either 20 mg SC twice daily for 10 days or 20 mg/m2 SC once daily for 14 days. Doses of clofarabine will be studied in a sequential dose escalation manner starting with 10 mg in cohorts of 3-6 patients. The clofarabine dose will be escalated to 20 and 30 mg with the option of deescalating the dose by 5 mg increments until the maximum tolerated dose (MTD) is determined. Once the MTD is reached we will expand the cohort in order to estimate efficacy. Inclusion criteria includes diagnosis of first relapse or refractory AML or high-risk MDS after one previous treatment, age 60 years or older, no prior exposure to cytarabine or clofarabine, ECOG performance status of 0-2, and adequate hepatic and renal function. The primary objective is to estimate the MTD of oral clofarabine when given with LDAC. Secondary objectives include determining the response rate, disease free survival and overall survival after therapy. We have currently enrolled 12 out of 39 anticipated patients.