tbuckley/cabot-search huggingface dataset:
Association of sex and adverse events (AEs) of adjuvant chemotherapy (ACT) in early stage colon cancer (CC): A pooled analysis of 28,636 patients (pts) in the ACCENT database.
Authors: Anna Dorothea Wagner, Axel Grothey, Thierry Andre, Jesse Dixon, Norman Wolmark, Daniel G. Haller, Carmen Joseph Allegra, Eric VanCutsem, Thomas J. George, Aimery De Gramont, Steven R. Alberts, Chris Twelves, Michael O'Connell, Leonard B. Saltz, Charles David Blanke, Guido Francini, Rachel Kerr, Richard M. Goldberg, Greg Yothers, Qian Shi
Journal: Journal of Clinical Oncology (2018)

3603 Background: Sex is one of several factors known to affect drug efficacy and toxicity. Preliminary data in different types of cancers suggest a higher toxicity of chemotherapy in women. Aim of this pooled analysis was to understand the clinical relevance of sex differences in toxicity of ACT in CC. Methods: The primary aim was to compare these major AEs: nausea, vomiting, stomatitis, diarrhea, leucopenia, neutropenia, anemia, thrombocytopenia, and neuropathy (pts receiving oxaliplatin) between men (M) and women (W) treated with ACT after curative resection. Severity of AEs was categorized as per NCI criteria. Comparisons were conducted by chi-squared test and logistic regression based on type of ACT, including fluoropyrimidine (5-FU) as single-agent, 5-FU + irinotecan (FOLFIRI), or 5-FU + oxaliplatin (FOLFOX). P < 0.001 was considered significant due to multiple comparisons. Results: AE data were available in 28,636 pts (54% M) from 26 studies. Overall, women were at greater risk for the majority of toxicities (see Table). Conclusions: Further investigations are needed to better understand the impact of sex on toxicity and efficacy of chemotherapy. Possible differences in perception do not explain the significant differences in neutropenia. These results suggest that sex-specific strategies for drug dosing and supportive care may need consideration. *Grade I-IV (III/IV) AE in % 5-FU (n = 22,770) FOLFOX (n = 3,655) FOLFIRI(n = 2,211) W M W M W M Nausea 57 (6.8) 49 (3.5) 33 (9.6) 29 (4.7) 77 (10) 66 (6.9) Vomiting 31 (5.1) 21 (2.6) 24 (9.0) 18 (4.7) 52 (9.3) 40 (6.0) Nausea/vomiting 59 (8.1) 51 (4.3) 36 (13) 32 (6.8) 80 (13) 70 (9.6) Stomatitis 30 (7.2) 24 (4.4) 16 (3.1) 16 (1.8) 32 (1.8) 27 (.87) Diarrhea 62 (20) 58 (16) 37 (21) 31 (15) 74 (21) 68 (16) Leucopenia 40 (5.6) 32 (3.1) 3.2 (2.3) 2.4 (1.4) 68 (11) 59 (7.4) Neutropenia 36 (16) 33 (11) $ (27) $ (18) 78 (40) 69 (26) Thrombocytopenia 5.6 (.25) 9.7 (.26) 26 (1.7) 30 (1.5) 17 (1.4) 21 (1.7) Anemia 33 (.53) 25 (.40) 37 (1.5) 41 (.47) Neuropathy 69 (18) 71 (15) * AEs with p < 0.001 are denoted by bold font; $ data with grade I-II were missing
Lenalidomide induction and maintenance therapy for transplant eligible myeloma patients: Results of the Myeloma XI study.
Authors: Graham H. Jackson, Faith Davies, Charlotte Pawlyn, David A. Cairns, Alina Striha, Anna Waterhouse, John Jones, Bhuvan Kishore, Mamta Garg, Cathy Williams, Kamaraj Karunanithi, Jindriska Lindsay, Matthew Jenner, Gordon Cook, Martin Kaiser, Mark Drayson, Roger G. Owen, Nigel Russell, Walter Gregory, Gareth John Morgan
Journal: Journal of Clinical Oncology (2017)

8009 Background: Immunomodulatory (IMiD) agents are effective therapies for multiple myeloma (MM), with Lenalidomide (Len) having fewer side effects than Thalidomide (Thal), enabling long-term treatment. The optimum IMiD induction and maintenance regimen are unknown. We therefore compared triplet induction regimens of Len vs Thal and examined the role of maintenance Len vs observation, enabling us to explore the interaction of Len induction with Len maintenance. Methods: Myeloma XI is a multicenter, randomized controlled trial for newly diagnosed MM, with pathways for transplant eligible (TE) and non-eligible patients. For TE patients the induction question compared Len or Thal plus cyclophosphamide and dexamethasone (CRD vs CTD) continued for a minimum of 4 cycles and to max. response. For patients with a suboptimal response there was a subsequent randomization to a proteasome inhibitor containing triplet or no further therapy prior to ASCT. A maintenance randomization at 3 months post ASCT compared Len till disease progression vs observation. 2042 TE patients underwent the induction randomization (CRD 1021, CTD 1021). After a median follow up of 36.3 months, 965 PFS and 415 OS primary endpoint events had occurred. Secondary endpoints included response and toxicity. Results: In TE patients, CRD induction was associated with deeper responses than CTD: ≥VGPR CRD 60% vs CTD 53%. This was associated with a significantly improved median PFS (HR 0.85, 95%CI 0.75, 0.96, CRD 35.9 months vs CTD 32.9, p=0.0116) and 3 year OS: 82.9% vs 77.0% (HR 0.77, 95%CI 0.63, 0.93, p=0.0072). Maintenance therapy with Len was associated with a significantly longer median PFS compared to observation (HR 0.47, 95%CI 0.38, 0.60) across all subgroups including patients with high-risk disease. Exploratory analysis across the TE pathway suggested that CRD induction with Len maintenance was optimum: 60 month PFS CRD-R 50.2%, CTD-R 39.1%, CRD-obs 18.5%, CTD-obs 23.4%. Conclusions: CRD was associated with deeper responses than CTD, and with a PFS and OS benefit. The best outcomes were associated with Len induction plus Len maintenance. Our findings support continuing Len therapy through induction until disease progression. Clinical trial information: NCT01554852.
Results of the phase II TRUST trial of induction treatment with FOLFOXIRI + bevacizumab (BV) followed by chemo-radiotherapy (CRT) plus BV and surgery in locally advanced rectal carcinoma (LARC).
Authors: Gianluca Masi, Sara Lonardi, Aldo Sainato, Piero Buccianti, Giacomo Allegrini, Angelo Martignetti, Caterina Vivaldi, Francesca Bergamo, Sabrina Montrone, Matteo Franceschi, Lorenzo Marcucci, Gianna Musettini, Francesca Battaglin, Gabriele Coraggio, Riccardo Balestri, Chiara Cremolini, Isabella Paladina, Lisa Salvatore, Vittorina Zagonel, Alfredo Falcone
Journal: Journal of Clinical Oncology (2016)

3615 Background: Induction chemotherapy (CT) is a promising option in LARC. FOLFOXIRI + BV is an effective treatment in metastatic colorectal cancer. Methods: This is a phase II multicentric single-arm single-stage trial. Primary endpoint was 2-year disease-free survival (DFS). Patients (pts) with LARC at < 12 cm from the anal verge, cN+ or cT4 or high risk cT3 (MRI criteria) underwent 6 cycles of FOLFOXIRI (irinotecan 165 mg/m2, oxaliplatin 85 mg/m2, folinate 200 mg/m2 and 5FU 3200 mg/m2 in 48 h) + BV (5 mg/kg) every 2 weeks followed by CRT (50.4 Gy + 5FU 225 mg/m2/day or capecitabine 825 mg/m2/bid continuously + BV 5 mg/kg on days 1, 15, 28). Surgery was planned 8 weeks after CRT. Results: We enrolled 48 pts. Main characteristics were: median age, 53 years (30-74); cT2/T3/T4, 4%/60%/36%; cN0/N+, 4%/96%. 46 pts completed induction CT: 1 patient (pt) died due to bowel perforation and sepsis and 1 discontinued CT after acute kidney injury. Main grade (G) 3/4 toxicities during induction were neutropenia (42%), febrile neutropenia (4.2%), diarrhea (12.5%). Clinical Response Rate (CRR) after induction was 77%. One pt underwent surgery after induction CT and 45 started CRT. After the first 13 pts, the protocol was amended and the schedule of capecitabine modified (800 mg/m2/bid 5 days/week) due to an excessive rate of G3 hand-foot syndrome (23%) and proctitis (23%). After amendment all pts completed CRT with acceptable toxicity: in particular G3-4 toxicities included only 6.2% proctitis. CRR after CRT was 78%. One pt had early progressive disease (PD) after CRT and died. 44 pts underwent surgery: low anterior resection 90%, abdomino-perineal resection 7%. R0 resection was achieved in 98% of pts. Early (90 days) post-surgical complication rate was 31% with 17% of anastomotic dehiscences, all solved. Pathologic complete response rate was 36%. At a median follow up of 21 months, 8 pts had PD (2 local recurrences) and the estimated 2y-DFS is 78%. Conclusions: Induction CT with FOLFOXIRI + BV followed by CRT is feasible and highly active in LARC. The rate of early post-surgical complications is not negligible. Preliminary results for DFS are promising. Clinical trial information: 2011-003340-45.
Influence of melanocortin-1 receptor (MC1R) polymorphisms on clinical outcomes of patients with metastatic melanoma harboring the BRAF mutation and treated with BRAF inhibitors.
Authors: Sabino Strippoli, Gabriella Guida, Anna Ferretta, Nicola Bartolomeo, Amalia Azzariti, Stefania Tommasi, Claudia Grieco, Anna Albano, Stefania Guida, Vito Lorusso, Michele Guida
Journal: Journal of Clinical Oncology (2016)

9574 Background: In the pigmentation of hair and skin a key role is played by the MC1R gene whose inherited variations are linked with a higher melanoma risk. In melanoma cells, MC1R has a central role because of its interaction with several intracellular signaling cascades such as the MAPK or mTOR pathways. Little heed has been paid to the role of its genetic polymorphisms in the management of metastatic melanoma. Our aim was to evaluate the effects of MC1R variants on the clinical outcomes of BRAF mutated patients treated with BRAF inhibitors. Methods: Fifty-three consecutive patients were evaluated according to their MC1R status (21 wild type and 32 with minor/major functional variants). First we explored eventual association between MC1R status and basal patient features. Than we evaluated the influence of MC1R status on therapeutic outcomes to anti BRAF inhibitors (ORR, PFS, OS). Finally, we studied the effect of vemurafenib in 2 BRAF V600 melanoma cell lines with and without MC1R variant. Results: Regarding the baseline patient features, we only found an association between MC1R polymorphisms and bone metastases (p 0.017). Moreover, MC1R variants were significantly associated with worse outcomes to BRAF inhibitors compared with MC1R wild type in terms of both ORR (59% vs 95% [p 0.011 in univariate, p 0.028 in multivariate analysis]) and PFS shorter than 6 months (72% vs 33% [p 0.012 in univariate, p 0.027 in multivariate analysis]). No significant difference was found in OS, probably due to the influence of further treatments. Data in vitro demonstrated a significantly different phosphorylation of Erk1/2 and p38 MAPK before and after treatment, associated with a greater increase of vemurafenib IC50 in cases of MC1R variant. Conclusions: Our data document, for the first time, detrimental effects of MC1R variants on BRAF inhibitor therapy. Moreover, these evidences concur to understand the resistance mechanisms to targeted therapy and may help to pinpoint new therapeutic strategies.
Safety and activity of topical 4% doxycycline foam (FDX104) in epidermal growth factor receptor inhibitor (EGFRI) induced skin toxicity.
Authors: Einat Shacham Shmueli, Ravit Geva, Nirit Yarom, Ayala Hubert, Rita Keynan, Tal Hetzroni Kedem, Meir Eini, Dov Tamarkin, Mitchell Shirvan
Journal: Journal of Clinical Oncology (2016)

10130 Background: Painful and pruritic acneiform rash is a common treatment-limiting side effect of antibody and small molecule EGFRIs used to treat various cancers. Absent an approved product, off-label doxycycline, a tetracycline analog, has been used to prevent rash. Oral doxycycline, however, may cause limiting systemic side effects Methods: We conducted a Ph 2, randomized, double-blind, multicenter study investigating the safety and efficacy of self-applied, twice-daily, FDX104 in 24 patients receiving cetuximab or panitumumab for metastatic colon cancer. Each patient acted as her/his own control by applying FDX104 to one side of the face and matching foam vehicle (placebo) to the other side, beginning 1 week prior to starting the EGFRI. Patients were evaluated until 4 weeks after EGFRI initiation. Rash was quantified by an independent dermatologist using a Global Rash Severity (GRS) scale and by study investigators using a modified MASCC EGFRI Skin Toxicity Tool (MESTT). Maximum-grade rash severity on each side of the face at any visit was used in all analyses Results: Overall, 79% of patients developed rash. The most prominent rash-preventative effect was seen in the patients with severe (grade 3) rash. The overall difference in GRS grade 3 rash favored the FDX104 treatment side: grade 3 rash developed in 9 patients (37.5%) on the placebo side, but only 4 patients (16.7%) on the FDX104 side (P< .05). Four patients had a 2-grade difference in GRS scoring (severe vs mild) between sides. The time from EGFRI treatment initiation to first grade 3 rash trended in favor of FDX104 (hazard ratio = 0.2; P= .096), as did the probability of remaining free of severe rash over time (P= .096). MESTT-based analyses had similar but nonstatistically significant results. FDX104 was associated with mild, transient, localized skin reactions in 6 patients Conclusions: In patients receiving antibody EGFRIs, topical FDX104 was well tolerated and safe. FDX104 applied to skin caused no systemic side effects and had clinically meaningful EGFRI rash prevention activity. Topical FDX104 has the potential to improve patient quality of life, EGFRI compliance, and cancer outcomes and warrants additional studies Clinical trial information: NCT02239731.
A population-based evaluation of demographics and survival in primary effusion lymphoma: SEER database analysis.
Authors: John Khoury, Christopher Willner, David Macari, Zhou Yu, Susanna S. Gaikazian, Michael J. Stender, Ishmael A. Jaiyesimi
Journal: Journal of Clinical Oncology (2018)

e19535 Background: Primary effusion lymphoma (PEL) is one of the least common of the AIDS-related lymphomas, accounting for less than 4% of cases. The optimal treatment for primary effusion lymphoma (PEL) remains unclear and there is a paucity of data regarding this neoplasm, which carries a uniformly poor prognosis. Antiretroviral therapy in addition to chemotherapy has shown to improve survival in a few small retrospective studies. Methods: Between 2002 and 2014, all cases of PEL were extracted from the population-based cancer registries of the Surveillance Epidemiology and End Results program (SEER). Instances of PEL were identified with the ICD-O-3 (9678) histological code. Frequency, demographics, and survival data were assessed using SPSS statistical software. Results: A total of 117 cases of PEL were identified. PEL was significantly more prevalent in men (89.7%) and in Caucasians (77.8%) with median age at diagnosis of 49 years. Median overall survival was 6 months; CI, 3.7 to 8.2 months. Of all PEL cases, 62.4% received chemotherapy and 37.6% did not. Those who received chemotherapy had an overall survival of 10 months when compared to subjects who did not receive chemotherapy (p = 0.002). Death was directly related to PEL in 40.2% of the cases. Disease-specific median overall survival was markedly higher (29.000 months) than that of the entire cohort. Multivariable analysis demonstrated that age and race were not associated with mortality. Chemotherapy was associated with decreased mortality risk (HR, 0.45; CI, 0.28 –0.74; p = 0.002) Conclusions: In confirmation of previously published data, the highest incidence of PEL was found in Caucasian males. Subjects who received chemotherapy were found to have improved overall survival outcome. Other factors not related to PEL were associated with early mortality in this population.
The impact of sleep disturbances (SD) on quality of life, psychological morbidity, and survival of advanced cancer patients (ACP) and caregivers (CG).
Authors: Fay J. Hlubocky, Tamara Sher, David Cella, Bonnie J. Yap, Mark J. Ratain, Jeffery Peppercorn, Christopher Daugherty
Journal: Journal of Clinical Oncology (2017)

10115 Background: SD have been described as a significant symptom burden for cancer patients and their caregivers. However, in advanced cancer, the prevalence of SD and its impact on the quality of life (QOL) and psychological morbidity of ACP over time has not been described. Methods: A prospective cohort of ACP participating in phase I trials was assessed at baseline (T1) and one month (T2) using psychosocial instruments: cognition (MMSE); depression(CES-D), state anxiety (STAI-S), QOL(FACIT-Pal), global health (SF-36). Semi-structured interviews evaluated SD patterns including: quality/latency, habitual efficiency, daytime dysfunction. Results: To date,152 subjects (76 ACP and 76 CG) have been separately interviewed at T1 and T2. For the total population: median age 61 (28-78y); 51% male; 100% married; 90% Ca; 64% &gt; HS educ; 52% GI dx; 51% income &lt; $65,000 yr; ACP median survival 7.9 months (0.41-18.2). At T1, 57% of ACP reported experiencing SD within the past week including: 55.6% insomnia, 44% nonrestorative sleep, 49% low energy, 48% daytime somnolence. For CG, 72% reported experiencing SD: 68% insomnia, 64% nonrestorative sleep, 69% fatigue, 66% daytime somnolence. At T2, rates remained consistent over time for both ACP and CG across time with the exception of increased insomnia at 61% and 76% respectively. After controlling for pain, mood, and fatigue, ACP with self-reported SD had higher STAI-S (33 ±11 v 29 ±8 , p = 0.02) and poor global health (54 ± 19 v. 64 ± 21, p = 0.01) at T2. CG with SD had higher STAI-S anxiety (39 ± 17 v 35 ± 13, p = 0.03) and poor global health (75 ±26 v 88±16, p = .0002) at T2.Regression analyses revealed ACP with self-reported insomnia had poorer FACIT-Pal QOL (59 ± 9 v 63 ± 10, p = 0.01) over time. Prior chemotherapy was associated with ACP SD (70% v. 33%, p = 0.02). Regarding prognosis, ACP with insomnia had shorter median survival (5.5 v. 7.2 months, p = 0.01). Conclusions: SD are prevalent among ACP participating in clinical trials and were associated with disease progression, QOL, and anxiety. Multidisciplinary supportive care interventions designed to address SD are warranted.
Vinorelbine plus capecitabine in a heavily pretreated HER2 negative metastatic breast cancer patient population: MCEPASTEBIN.
Authors: Alfredo Enrique Torres, Charles L. Vogel, Jeremy Ramdial, Reshma L. Mahtani, Ana Sandoval-Leon
Journal: Journal of Clinical Oncology (2018)

e13122 Background: Metastatic breast cancer (MBC) is viewed as essentially incurable. Even though some studies have shown survival benefit for combination chemotherapy they were not specifically designed to address the superiority of combination versus sequential chemotherapy. A recent Cochrane review showed that there is no difference in overall survival between combination and sequential chemotherapy and combination therapy was associated with higher rates of neutropenic fever. The combination of vinorelbine with capecitabine was not included in this review. Several phase I and phase II studies have been published using this combination and most of them show this regimen to be well tolerated and effective. Most of these studies have been using this combination as first or second line. Our specific aim was to determine if the combination of vinorelbine with capecitabine in heavily pretreated patients with metastatic Her2 negative breast cancer was effective and tolerable. Methods: We retrospectively analyzed the charts of women with human epidermal growth factor receptor (HER2) negative MBC treated with vinorelbine 22.5mg/m2 IV on day 1 and 8 combined with capecitabine 1 gram PO BID for 14 consecutive days of 21 day cycles. Patients were treated on average with 4 lines of chemotherapy. Data on clinical outcomes and patients characteristics were collected and evaluated. Results: A total of 67 patients received the combination of vinorelbine with capecitabine and 2 patients among the 67 had two separate exposures giving an evaluable sample size of 69. Clinical benefit rate, defined as complete response, partial response or stable disease ≥ 6months, was 63.76%. Median progression free survival (PFS) time was 6.2 months and overall survival 35.47 months from start of VINOCAP therapy. The most common grade 3-4 toxicity was neutropenia in 10% of cases. Dose had to be reduced in 18% of the patients due to toxicity. Subjectively the regimen was very well tolerated. Conclusions: The combination of vinorelbine with capecitabine appears to be active in women with MBC. Especially encouraging was the efficacy of VINOCAP in patients treated as fifth or greater line of chemotherapy.
Abstract 18152: Targeted Mitochondrial Protection Increases the Efficacy of Stent Revascularization for Restoring Blood Flow, Tissue Oxygenation and Kidney Function in Patients With Atherosclerotic Renal Artery Stenosis
Authors: Ahmed Saad, Sandra Herrmann, Alfonso Eirin, John Woollard, Michael McKusick, Lilach Lerman, Stephen Textor
Journal: Circulation (2016)

Background: Atherosclerotic renal artery stenosis (ARAS) reduces renal blood flow (RBF) and GFR and amplifies stenotic kidney (SK) hypoxia. Renal revascularization with percutaneous transluminal re...
MIBG followed by haploidentical stem cell transplant with post transplant cyclophosphamide in relapsed/refractory neuroblastoma.
Authors: Shruti Kohli, Neha Rastogi, Sagar Nivargi, Yogi Raj Chopra, Dhwanee Shardul Thakkar, Ishita B Sen, Satyendra Katewa, Ruchira Misra, Satya Prakash Yadav
Journal: Journal of Clinical Oncology (2016)

e22002 Background: Relapsed/Refractory Neuroblastoma(RR-NB) outcomes are dismal. One study of Iodine-131-labled MIBG (131I-MIBG) and T-cell depleted haploidentical Stem Cell Transplant (SCT) has shown progression-free survival of 38% at 3 years in RR-NB. We hypothesize that T-cell replete haploidentical SCT with Post Transplant cyclophosphamide (PT-Cy) may be a cheaper and equally effective option. Methods: 5 children (ages 2-15 years) who had relapsed (9-30 months) after autologous SCT for NB were enrolled after informed consent. All had stage 3 or 4 disease at relapse. All were given 2 cycles of Bortezomib, Cyclophosphamide (Cy), Etoposide and Vincristine before MIBG therapy. One patient opted against MIBG. The remaining 4 received MIBG therapy (dose 4-12 mCi/kg). One with complete remission(CR) underwent haploidentical SCT (haplo-SCT). 3 children with partial response (PR) underwent autologous-SCT (auto-SCT). Of these, 2 underwent further haplo-SCT 45 and 60 days respectively after auto-SCT, 1 had progressive disease (PD) and was off protocol. The conditioning regimens and treatment details for haplo and auto-SCT are described in Table I. For GVHD prophylaxis PT-Cy 50 mg/kg was given on day+3 and +4 along with tacrolimus and MMF from day+5. Results: Post induction chemotherapy one with CR underwent MIBG and Haplo-SCT and died of veno-occlusive disease. The remaining three had PR and underwent MIBG and Auto-SCT. One developed progressive disease after auto-SCT and died. Remaining two underwent further haplo-SCT of whom one died on day+17 with CNS disease and other is disease free at day+42. Conclusions: MIBG with Haplo-SCT with PT-Cy is a feasible option in the developing world for RR- NB. Further studies with longer follow up are needed. Patient 1 2 3 4 MIBG Y Y Y Y Auto-SCT Y Y Y N Conditioning CEM CEM Mel - CD34 dose/kg 4.5 x106 10.6 x106 1.9 x106 - Disease status PD PR PR CR Haplo-SCT N Y Y Y Conditioning - Flu Cy Mel Flu Cy TBI Flu Cy Mel Stem cell source - PB PB PB CD34 dose/kg - 5.9 x106 3.08x106 10.9 x106 Neutrophil engraftment Day - +14 +19 +16 GVHD - No Grade 1 No Disease status PD PD CR CR Outcome D D Alive D Y-yes N-No CEM- Carboplatin, Etoposide, Melphalan PB- Peripheral blood D-Died