tbuckley/cabot-search huggingface dataset:
Randomized phase II trial comparing docetaxel with or without low-dose metronomic oral cyclophosphamide in first-line treatment of non-triple-negative advanced breast cancer.
Authors: Leiping Wang, Jian Zhang, Zhong Hua Wang, Biyun Wang, Jun Cao, Fangfang Lv, Sheng Zhang, Shao Zhimin, Xi-Chun Hu
Journal: Journal of Clinical Oncology (2014)

1041 Background: Oral metronomic chemotherapy may target tumor cells indirectly via antiangiogenic activity, restoration of anticancer immune response, or induction of tumor dormancy. This phase II study (NCT01526499) aims to evaluate the efficacy of metronomic oral cyclophosphamide in addition to docetaxel as first-line therapy. Methods: Eligible patients with ER or PR positive or HER-2-overexpressed ABC who previously untreated were randomly assigned to receive docetaxel 75 mg/m2on day 1 with or without continuous oral cyclophosphamide 50mg daily in a 21-day cycle. Patients with HER-2-overexpressed tumors also receive trastuzumab. All patients received docetaxel until disease progression or unacceptable toxicity or withdrawal of consent. Maintenance endocrine and/or trastuzumab were allowed. The primary endpoint was PFS. Results: Between Dec 2011 and Nov 2012, 31 patients were randomized to docetaxel (T) group while 35 to cyclophosphamide plus docetaxel (Metro-TC) group. The majority of the patients (83.3%) were hormonal receptor positive; 31.8% were HER2 over-expressed; 84.8% had visceral metastasis and 48.5% had ≥3 metastatic organ sites. Patients’ characteristics were well balanced. Median treatment cycles of docetaxel for both groups were eight cycles. In intention-to-treat population with median follow-up of 18 months, median PFS was statistically longer in the Metro-TC group ( not reached) than it was in the T group (13.6 months, 95%CI, 7.0 to 20.2) (P =.04). Median OS had not been reached. The ORR were 51.6% (16/31) in the T and 71.4% (25/35) in Metro-TC group, respectively (P =.09). There was no significant difference of grade 3/4 toxicities between the two groups. Adverse effects were mainly docetaxel-related, including grade 3/4 neutropenia (100%) and febrile neutropenia (n=19, 29.2%). The only significant difference between the two treatment was mucositis (all grade, 10% versus 43%, P=0.003). Conclusions: The addition of metronomic cyclophosphamide to standard chemotherapy as first-line treatment for non-triple-negative ABC shows a beneﬁt in PFS without significant increase in toxicity. Clinical trial information: NCT01526499.
Allogeneic hematopoietic cell transplantation after reduced intense conditioning as adoptive cell therapy in resistant metastatic colorectal carcinoma. The European experience
Authors: M. Aglietta, L. Barkholt, D. Caravelli, C. Minotto, A. Capaldi, B. Omazig, G. Ciccone, D. Niederwieser, O. Ringden, T. Demirer
Journal: Journal of Clinical Oncology (2006)

3596 Background: Allogeneic reduced intense conditioning regimens decreased morbidity and mortality related to hematopoietic stem cell transplantation (HCT), retaining a powerful graft versus tumor effect (GVT). On this basis, it became possible to explore the existence of alloreactivity in solid tumors. A GVT effect was described in metastatic colorectal cancer (CRC). Methods: We report the data on 35 patients with CRC treated with non-myeloablative allogeneic HCT in Europe. Median time from the diagnosis of metastatic disease to transplant was 16 (4–47) months; 25 patients (67%) received at least 2 lines of therapy before transplant. Disease status at transplant was progressive disease (PD) in 31 patients (80%), stable disease (SD) in 6 (14%) and partial response (PR) in 2 (6%). Patients were treated according to different nonmyeloablative regimens. All but one patient received allogeneic peripheral hematopoietic cells [median CD 34+ cells/kg was 6.7 × 10 6 (2,5–55), median CD3 + cells/kg was 4.9 × 10 8 (0,11–33)] from HLA identical familiar donors. GVHD prophylaxis consisted of cyclosporine A (CyA) + Mycophenolate Mofetil in 24 (68%), of CyA + methotrexate in 6 (25%) and other CyA regimens in the others (18%). Results: Myelosuppression was mild and all patients engrafted with a median donor chimerism of 90% (45–99) on CD 3 cells on day +60. Transplant-related toxicities were limited. Grades II-IV acute GVHD occurred in 18 patients (51%) and chronic GVHD in 6 patients (25%). Transplant-related mortality was the cause of death in 4 patients (11%). As best tumor response we observed: 1 complete response (3%), 8 PRs (20%) and 9 SDs (29). Overall median survival from the date of transplant was 198 days (6–1020); median overall survival for the responding patients was 353 days (113–1020). Conclusions: Allogeneic HCT after RIC is safe and feasible in metastatic CRC. The results obtained compared favorably with those observed in patients with hematologic malignancies or metastatic CRC beyond second line in terms of transplant-related complications and tumor response respectively. Thus a study of allogeneic cell therapy in a less advanced patient cohort is warranted. No significant financial relationships to disclose.
Nivolumab in patients with DNA mismatch repair deficient/microsatellite instability high metastatic colorectal cancer: Update from CheckMate 142.
Authors: Michael J. Overman, Sara Lonardi, Francesco Leone, Raymond S. McDermott, Michael A. Morse, Ka Yeung Mark Wong, Bart Neyns, Joseph L. Leach, Pilar Garcia Alfonso, James J. Lee, Andrew Hill, Heinz-Josef Lenz, Jayesh Desai, Rebecca A. Moss, Z. Alexander Cao, Jean-Marie Ledeine, Hao Tang, Scott Kopetz, Thierry Andre
Journal: Journal of Clinical Oncology (2017)

519 Background: Approximately 4% of metastatic colorectal cancers (mCRCs) are associated with high microsatellite instability (MSI-H), indicating a deficient DNA mismatch repair (dMMR) system. dMMR/MSI-H CRC exhibits an increased tumor neoantigen load and immune cell infiltration and is hypothesized to be targetable by immune checkpoint inhibitors. CheckMate 142 (NCT02060188) evaluates the efficacy and safety of nivolumab (nivo) in patients (pts) with dMMR/MSI-H mCRC. Methods: Pts with dMMR/MSI-H mCRC who progressed on/were intolerant to ≥1 prior line of therapy received nivo 3 mg/kg (nivo 3) every 2 weeks (Q2W). The primary endpoint was objective response rate (ORR) per investigator (INV). The secondary endpoint was ORR per independent radiology review committee (IRRC); exploratory endpoints included safety, PFS, OS, and efficacy in biomarker-defined populations. Results: Among pts treated with nivo 3 Q2W (N = 74), 84% had received ≥2 prior lines of therapy. ORRs were 31% (INV) and 27% (IRRC); disease control rates were 69% (INV) and 62% (IRRC). The median time to response was ≈2.7 mo (INV/IRRC). PFS rates at 12 mo were 48.4% (INV) and 45.6% (IRRC). The duration of response and OS medians were not yet reached; OS rates were 83.4% (6 mo) and 73.8% (12 mo). Responses were observed in pts regardless of tumor programmed death-1 ligand 1 (PD-L1) expression level or BRAF or KRAS mutation status and were observed in pts with or without a history of Lynch syndrome (Table). Grade 3–4 treatment-related adverse events (TRAEs) occurred in 20% of pts. TRAEs leading to discontinuation included acute kidney injury, increased ALT, colitis, and stomatitis (1 each). No treatment-related deaths occurred in this arm. Conclusions: Nivo showed durable responses and disease control in heavily pretreated pts with dMMR/MSI-H mCRC. Treatment was well tolerated, with no new safety signals. Clinical trial information: NCT02060188. [Table: see text]
Awareness among patients with cancer of the harms of continued smoking.
Authors: Lawson Eng, Devon Alton, Jiahua Che, Yuyao Song, Jie Su, Delaram Farzanfar, Rahul Mohan, Olivia Krys, Tom Yoannidis, Robin Milne, M Catherine Brown, Ashlee Vennettilli, Andrew J. Hope, Doris Howell, Jennifer M. Jones, Peter Selby, Wei Xu, David Paul Goldstein, Meredith Elana Giuliani, Geoffrey Liu
Journal: Journal of Clinical Oncology (2017)

179 Background: Smoking cessation is becoming an integral part of cancer survivorship. To help improve survivorship education, clinicians need an understanding of patient knowledge of the harms of continued smoking. Methods: Patients with various cancer subtypes were surveyed with respect to self-awareness of the harms of continued smoking on cancer outcomes. Multivariable logistic regression models assessed factors associated with the level of awareness. Results: Among 985 patients, 23% smoked at diagnosis; 34% quit &gt; 1 year prior to diagnosis; 25% had lung, 30% had head and neck cancers; 77% received curative therapy. Many patients reported being unaware that smoking can negatively impact cancer surgery (65%), radiation (74%), chemo outcomes (64%), treatment efficacy (70%), cancer prognosis (54%) and second primary development (52%). Among all patients, those smoking at diagnosis were significantly more likely to be unaware of radiation (aOR = 1.73, 95% CI [1.16-2.57]) and chemo (aOR = 2.10 [1.17-3.79]) toxicities, cancer prognosis (aOR = 1.63 [1.16-2.29]) and second primary risk (aOR = 1.61 [1.14-2.26]). Those with poorer health status were more likely unaware of effects on prognosis (aOR = 1.56 [1.18-2.08]) and second primaries (aOR = 1.54 [1.14-2.08]). Patients with non-tobacco related cancers (non-TRCs) were more likely unaware smoking impacts cancer surgery (aOR = 1.45 [1.04-2.04]) and radiation (aOR = 1.37 [1.01-1.85]). Among smokers at diagnosis, those with non-TRCs (aOR = 4.00 [1.45-11.11]) were more likely unaware smoking can impact chemo outcomes. Awareness was not associated with stage, second-hand smoke exposure, cessation or interest in a smoking cessation program (SCP), but was associated with patients believing that a SCP would be beneficial to their health (aORs = 2.33-4.35, P &lt; 0.03). Among smokers at diagnosis, believing that a SCP is beneficial (51%) was associated with both interest in an in-patient (aOR = 4.65 [2.15-10.03]) and ambulatory (aOR = 4.08 [2.14-7.79]) SCP. Conclusions: Many cancer patients were unaware of the harms of continued smoking; mainly smokers at diagnosis and those with non-TRCs. Patient education should focus on emphasizing awareness, which may help improve patient interest in smoking cessation.
TabPRO trial: Tablet-based real-time detection of patient-reported outcomes during adjuvant outpatient chemotherapy for breast cancer.
Authors: Michael R. Mallmann, Christian M. Domroese, Christine Fuhrmann, Fabinshy Thangarajah, Lena Leitzen, Angela Ulhaas, Frederik Bach, David Engelhardt, Esther D. Beier, Mignon-Denise Keyver-Paik, Christoph Coch, Christina Kaiser, Alina Abramian, Benno Nuding, Wolfram Malter, Stefan Kraemer, Marina Wirtz, Christian Rudlowski, Oliver Zivanovic, Walther C. Kuhn
Journal: Journal of Clinical Oncology (2015)

TPS9640 Background: Current symptom inquiry during adjuvant chemotherapy is based on symptom reporting at regular intervals, usually at the start of the subsequent cycle of chemotherapy or by telephone interviews during chemotherapy cycles. Consequently there exists a time lag between occurrence of symptoms, reporting by the patient and initiation of side-effect directed therapy. In contrast, a real-time reporting of symptoms might fasten reaction towards side effects and thus improve patient care. Methods: This prospective multicenter trial determines the feasibility of an App-based query system to collect patient-reported outcomes (PRO) during outpatient adjuvant chemotherapy for breast cancer and to treat side effects during chemotherapy in real-time. The system includes an App-based symptoms assessment software for patients and an either Tablet- or computer-based symptoms-control software for physicians and health-care professionals offering a daily checkup of symptoms using a visual and intuitive App-based symptom assessment. Thus far, all 57 anticipated patients that are treated with adjuvant therapy for breast cancer in the participating trial centers have been enrolled. We evaluate all chemotherapy-related symptoms in terms of frequency, severity, both association with chemotherapy cycles or patient characteristics and course during chemotherapy on at least a daily basis. Moreover, we evaluate time of reaction between reporting of PRO by the patient and both assessment and contacting by the physician. We evaluate the frequency of intervention as well as satisfaction with such a system by both patients and physicians. Electronic tablet-based PRO might increase efficiency of data collection and transmission, the patient-physician communication and consecutively patient compliance. Due to early intervention this type of outcome-monitoring might help to minimize chemotherapy-induced side effects by a rapid reaction to the reported symptoms. Consequently the TabPRO trial with its daily reporting of PRO has the potential to change the current assessment of chemotherapy-related side effects and to optimize patient care during outpatient chemotherapy. Clinical trial information: NCT01991691.
Prospective analysis of expression of circulating levels of matrix metalloproteinase-9 (MMP-9) in the serum of patients with primary central nervous system lymphoma (PCNSL)
Authors: A. F. Hottinger, B. Gu, M. Fleisher, L. E. Abrey, E. Holland, L. M. Deangelis, A. Hormigo
Journal: Journal of Clinical Oncology (2006)

1532 Background: Matrix metalloproteinases have been associated with angiogenesis, tumor infiltration and metastases formation in systemic lymphoma. Disease status in PCNSL is determined by brain MRI; however it may be inconclusive and non-invasive tests to evaluate disease status would be useful. This study was designed to determine whether circulating levels of MMP-9 could be related to disease status in PCNSL. Methods: Circulating levels of MMP-9 were determined by ELISA and correlated with disease status assessed by MRI in a prospective longitudinal study. The disease status was classified as no evidence of disease (CR) versus active disease (AD). Results: We enrolled 18 PCNSL patients and obtained 93 blood samples (median 6 per patient, range 1–10) from August 2002 to December 2005. When in CR (12 patients, 59 samples), the mean MMP-9 level was 205.5 ± 19.1 ng/ml (median 162.3 ng/ml, range: 35.9–649.1 ng/ml). MMP-9 levels were significantly higher in AD (16 patients, 34 samples), with a mean MMP-9 of 638.2 ± 140.7 ng/ml (median 287.5 ng/ml, range 24.7–3340.6 ng/ml) (p = 0.0001). Paired samples obtained before and after therapy were obtained in 10 patients. Patients in AD had a mean of 1223.9 ± 336.5 ng/ml (median 770.1 ng/ml, range 284.1–3340.6 ng/ml) before treatment and levels fell to a mean of 143.5 ± 38.4 ng/ml (median 86.7 ng/ml, range 28.1–356.5 ng/ml) (p = 0.005) when CR was reached. During follow-up, 4 of the 18 patients developed recurrent disease (total 5 recurrences). MMP-9 levels increased from 154.22 ± 34.9 ng/ml (median 162.4 ng/ml, range 64.5–260.3 ng/ml) to 324.4 ± 98.5 ng/ml (median 251.5 ng/ml, range: 159.5–709.7 ng/ml) (p = 0.14) at relapse. Conclusions: PCNSL patients in CR have circulating MMP-9 levels that are significantly lower than in patients with AD. A significant drop in MMP-9 was seen after treatment compared to baseline. MMP-9 levels increased with disease recurrence but did not reach statistical significance in this small population. MMP-9 has the potential to complement neuroimaging to confirm remission or progression. No significant financial relationships to disclose.
Clinical outcomes and late toxicity of hypofractionated intensity-modulated radiotherapy for high-risk prostate cancer.
Authors: Michael Wang, Robert Pearcey, Nadeem Pervez, Don Yee, Alina Mihai, Samir Patel, John Amanie, Matthew Parliament, Albert Murtha, Sunita Ghosh, Marc Mackenzie, Colin Field, Nawaid Usmani
Journal: Journal of Clinical Oncology (2017)

56 Background: Since prostate cancer has intrinsic high radiation-fraction sensitivity, hypofractionated radiotherapy (HFRT) could offer treatment advantages. However, dose-escalated HFRT may increase risks of late genitourinary (GU) and gastrointestinal (GI) toxicity. Intensity-modulated radiotherapy (IMRT) can potentially deliver dose-escalated HFRT without increasing late toxicities. This study’s acute toxicity data was previously published. We now present five-year efficacy results and late toxicity data for prostate cancer patients treated with HFRT using IMRT. Methods: From 2005-2012, our Phase II prospective study enrolled one hundred patients with either high risk disease (one or more of: Stage ≥ T3, Gleason ≥ 8, or PSA ≥ 20 ng/mL) or high tier intermediate risk disease (Gleason 7 and PSA ≥ 15 ng/mL). All patients received HFRT using IMRT in 25 daily fractions. Sixty patients received 68 Gy to the prostate and proximal seminal vesicles, with simultaneous integrated boost (SIB) of 45 Gy to pelvic lymph nodes and distal seminal vesicles. Forty patients received 68 Gy to the prostate, and a SIB of 50 Gy to pelvic lymph nodes and seminal vesicles. Adjuvant hormonal therapy was given for two to three years. Biochemical failure was determined by the Phoenix definition. Late toxicity scores were recorded every 6 months after completing RT. Results: Median age of patients was 67 years. 33% had Stage ≥ T3, 52% had Gleason ≥ 8, and 44% had PSA ≥ 20 ng/mL. After a median follow-up of 5.4 years, median PSA at last follow-up was 0.10 ng/mL. Five-year biochemical control rate (BCR) was 91.8%, five-year progression-free survival (PFS) was 92.8%, and five-year overall survival (OS) was 88.7%. Five-year cumulative incidence of Grade ≥ 3 GU and GI toxicity were 13.0% and 16.7% respectively. At the five-year efficacy endpoint, ongoing Grade ≥ 3 GU and GI toxicity were 1.9% and 0% respectively. Conclusions: Dose-escalated HFRT using IMRT results in favourable five-year BCR, PFS, and OS for patients with localized high-risk prostate cancer, and is well-tolerated with acceptable late GU and GI toxicity. These findings support ongoing Phase III trials that are assessing the clinical use of IMRT-based HFRT. Clinical trial information: NCT00126802.
Phase I and pharmacokinetic study of sorafenib in Kaposi sarcoma.
Authors: Thomas S. Uldrick, Kathleen Wyvill, Cody Peer, Mark Niccolo Polizzotto, Deirdre O'Mahony, Wendy Bernstein, Karen Aleman, Seth M. Steinberg, David J. Venzon, Stefania Pittaluga, Richard F. Little, William Douglas Figg, Robert Yarchoan
Journal: Journal of Clinical Oncology (2013)

10588 Background: Kaposi sarcoma (KS) is a multifocal angioproliferative disorder. VEGFR2-3, PDGFR and c-kit are implicated in KS pathogenesis and inhibited by sorafenib (So). KS is commonly HIV-associated. The antiretroviral drug ritonavir (R) inhibits CYP3A4, and may affect So metabolism and tolerability. Methods: We performed a phase I study of So in KS. HIV+ patients (pts) were eligible if on combination antiretroviral therapy (cART) for &gt;3 months with progressive KS or &gt;4 months with no KS regression. Dose level 1 for pts on R-containing cART (R1) was So 200 mg daily, for pts not receiving R (NR1) So 200 mg every 12 hours. Treatment cycles were 21 days. So pharmacokinetic assessment performed cycle 1 day 8. Adverse event (AE) grade (Gr) by CTCAE v3.0 (2006-10) and v4.0 (2011-12). KS response graded by modified ACTG criteria. Results: 10 pts, R1 (8), NR1 (2). Baseline characteristics: median (med) (range) age 49 (35-72), CD4 in HIV+ 500 cells/uL (35, 747), time on cART 9 months (3.5, 27), previous KS therapies 2 (0-5). 9 HIV-infected, 8/9 HIV viral load &lt;50 copies/mL. 6 had KS-associated edema. Med number cycles 4 (1, 13). Common AE at least possibly attributable to So: anemia, AST/ALT elevation, lipase elevation, hypertension, proteinuria, fatigue, infection, voice alteration. Dose-limiting toxicities (DLT): R1- Gr3 asymptomatic elevated lipase (1), Gr4 thrombocytopenia (1, likely due to multicentric Castleman disease); NR1- Gr3 hand-foot syndrome not resolved by week 6 (1). Other Gr 3-4 AE: R1- hand-foot syndrome (1), Gr3 thrombocytopenia (1), Gr3 transient cerebral ischemia (1), Gr3 hypertension (1); NR1- Gr3 hypertension (2). Best response: partial response (PR) (2), stable disease (SD)(5), progressive disease (1), not evaluable (2). Med duration SD 12 weeks (5, 33). 5/6 with KS-associated edema had objective decrease in edema. R was not associated with clear difference in So C Max or AUC at steady state. Conclusions: Preliminary estimate of PR or better is 20%. Even in some cases where KS did not respond, KS-associated edema improved. However, So was relatively poorly tolerated, with DLT observed at R1 and NR1, and these doses did not yield better responses than established therapies. Additional studies evaluating R’s effect on So metabolites are warranted. Clinical trial information: NCT00287495.
Pertuzumab (P) with trastuzumab (T) and chemotherapy (CTX) in patients (pts) with HER2-positive metastatic gastric or gastroesophageal junction (GEJ) cancer: An international phase III study (JACOB).
Authors: Josep Tabernero, Paulo Marcelo Hoff, Lin Shen, Atsushi Ohtsu, Ron Yu, Jennifer Eng-Wong, Yoon-Koo Kang
Journal: Journal of Clinical Oncology (2013)

TPS4150 Background: Human epidermal growth factor receptor 2 (HER2) is overexpressed in ~20% of gastric cancers. Specific targeting of HER2 by T in combination with CTX has demonstrated significantly improved overall survival (OS) vs CTX in pts with advanced gastric or GEJ cancer (Bang Lancet 2010). In HER2-positive 1L metastatic breast cancer the combination of T plus docetaxel with a second HER2-targeted antibody, P, demonstrated significant improvement of progression-free survival (PFS) and OS vs placebo+T+docetaxel (Baselga NEJM 2012; Swain SABCS 2012). Based on these positive findings with HER2-targeted therapies in gastric and breast cancer, JACOB, a double-blind, placebo-controlled, randomized Phase III study, is designed to evaluate efficacy and safety of P+T+CTX in pts with HER2-positive 1L metastatic gastric or GEJ cancer. Methods: Pts will be randomized 1:1 to receive P+T+cisplatin+fluoropyrimidine or the same regimen replacing P with placebo, q3w (P: 840 mg; T: 8 mg/kg first dose, then 6 mg/kg; cisplatin: 80 mg/m 2 ; 5-fluorouracil: 800 mg/m 2 /24 h given continuously for 120 h or capecitabine: 1000 mg/m 2 bid for 14 days). P/placebo+T will be given until progressive disease (PD) or unacceptable toxicity. On or before Cycle 6, CTX should only be discontinued for PD or unacceptable toxicity. Continuation of CTX after Cycle 6 is at the discretion of pt and physician. Randomization will be stratified by region (Japan vs North America/Western Europe/Australia vs Asia [excluding Japan] vs South America/Eastern Europe), prior gastrectomy, and HER2-positivity (IHC 3+ vs IHC 2+ and ISH+). Primary endpoint: OS; secondary endpoints include PFS, objective response rate, duration of response, clinical benefit rate, safety, pharmacokinetics of P, and patient-reported outcomes. Tumor and blood samples for biomarker evaluation will be collected. The study is estimated to have 80% power to detect a significant improvement in OS at a two-sided α-level of 5% (HR=0.777), with ~502 deaths required for the primary analysis. Target enrollment is 780 pts from ~200 sites and 35 countries; FPI is planned for April 2013. NCT01774786 Clinical trial information: NCT01774786.