bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of a 1-day 3-drug antiemetic regimen for prevention of acute and delayed nausea and vomiting induced by moderately emetogenic chemotherapy
Authors: Grunberg S. M. , Dugan M. , Muss H. B. , Wood M. , Burdette-Radoux S. , Weisberg T. 
Published: March 2020

9111 Background: Serotonin antagonists, NK-1 antagonists (NKA) and corticosteroids (C) have all shown efficacy against chemotherapy-induced nausea and vomiting. However these agents are commonly used in cumbersome and inconvenient multiple day regimens that can also raise questions of compliance. Palonosetron is a serotonin antagonist with a 40 hour half-life, requiring only one dose for several days of exposure. Single high doses of NKA and C can also be used to simulate drug exposures achieved with a multiple day regimen. We have therefore evaluated a 1-day 3-drug antiemetic regimen for 5 day efficacy against moderately emetogenic chemotherapy. Methods: Patients with solid tumors receiving their first cycle of cyclophosphamide and/or doxorubicin were eligible to receive a single pre-treatment dose of palonosetron 0.25 mg IV/dexamethasone 20 mg PO/aprepitant 285 mg PO. Nausea and vomiting were evaluated over the following 5 days with a patient diary including vomiting episodes, use of rescue medication, and daily nausea visual analogue scale (VAS). Patients were urged to begin rescue medication for nausea, vomiting, or related discomfort. Endpoints included Complete Response (CR) (no emesis or rescue), No Emesis (NE), and No Significant Nausea (NSN) (VAS<25) during the acute period (A) (Day 1), the delayed period (D) (Days 2–5), and the overall period (O) (Days 1–5). Adverse events were recorded and tabulated for at least 14 days. Results: 32 of 40 planned patients have been entered on study. 31 women and 1 man with breast cancer receiving adjuvant chemotherapy with median age 52 years (range 34–74) have been treated and all are evaluable. CR for A/D/O was 78%/59%/50%. However NE for A/D/O was 100%/97%/97%, and NSN for A/D/O was 75%/62%/56%. Only 8 patients had more than one day of Significant Nausea. The most common treatment-related adverse events were fatigue and mild headache. Conclusions: A 1-day 3-drug antiemetic regimen is feasible and effective, and should be tested against a multiple day standard antiemetic regimen. [Table: see text]
High rates of psychosocial stress among Hispanic breast cancer survivors
Authors: Apollo A. J. , Crew K. D. , Campbell J. , Greenlee H. , Jacobson J. S. , Grann V. , Raptis G. , Ortiz Y. , Hershman D. L. 
Published: March 2020

9113 Background: Due to early detection and improved treatments, women with breast cancer are living longer. We conducted a survey of attitudes about physical health, psychosocial issues, and health-related behaviors among female breast cancer survivors. Methods: Consecutive women with early-stage breast cancer who were ≥3 months post-completion of primary treatment and had no evidence of residual disease were asked to complete a 127-item self-administered questionnaire assessing physical/emotional health, complementary/alternative medicine use, and employment/financial concerns. Baseline demographic and clinical data were collected, including stage, tumor characteristics, and treatments. Endpoints were differences in responses between Hispanic and white patients on a 5-point scale, or dichotomized for each item. Results: Of 133 respondents, 66 were white and 67 were Hispanic. Their median age was 54 (26–90) years, and their median time since diagnosis was 3 (1–20) years. Compared to whites, Hispanic patients were younger (age <45, 34% vs. 9%, p=0.01), less educated (40% vs. 5% not completing high school, p<0.0001), and more likely to have a yearly household income <$10,000 (58% vs. 7%, p<0.0001). Hispanics were more likely than whites to report depression (31% vs 8%, p=0.0008) and depression-related symptoms and stressors such as: anorexia, pain, financial stress, and infidelity by spouse ( Table 1 ). Hispanics were also more likely to have religious beliefs that helped them cope with cancer. Differences between groups in fatigue, memory loss, and anxiety were not statistically significant. Conclusions: Our study suggests that Hispanic breast cancer survivors may have higher rates of depression and psychosocial stressors than white women. Further research is warranted to assess factors that contribute to depression in cancer survivors, and interventions to diagnose and treat it effectively. [Table: see text] No significant financial relationships to disclose.
Risk assessment model for first-cycle chemotherapy-induced anaemia (CIA) in patients with solid tumours (ST): DELFOS Study
Authors: López-Pousa A. , Rifà J. , Casas Fernández de Tejerina A. , González Larriba J. L. , Iglesias C. , Gasquet J. A. , Carrato A. 
Published: March 2020

9122 Background: CIA, a major side effect of systemic cancer chemotherapy, is directly associated with concomitant morbidity, mortality and costs, and therefore has a strong impact on both patient health and healthcare systems. The objective of the present research study is to determine a predictive model for first-cycle CIA in patients with ST in Spain. This will help to establish appropriate protocols in routine patient care, hence improving clinical decision making. Methods: Data were obtained from the DELFOS Study, a multicentre non- interventional prospective-cohort study in Spain. This study has completed enrolment and data were available for this planned analysis. To obtain the predictive logistic regression model (LRM), the hierarchical principle was followed as a way to enable results replication. The model was implemented for CIA defined as anaemia grade = 2 (haemoglobin [Hb]<10 mg/dL). Anaemic patients at baseline according to this criterion were excluded from the studied sample to avoid bias. A receiver operating characteristics (ROC) Curve was used to determine the model's sensitivity and specificity. Results: A total of 1,140 pts (57.3 % female; mean age: 58 yrs [SD: 12]; ECOG = 2) with ST (breast, 38.1%; lung 17.5%; colorectal, 14.3%; other 30.1%) and baseline Hb>10mg/dL were included from 88 Spanish medical oncology health centres. The LRM obtained predicting CIA (pChi-sq < 0.0005) contained the following factors: gender, baseline haemoglobin, platinum-based chemotherapy (PBC) and baseline bilirubin. Risk factors and size effects included: male gender (p=0.003, OR=2.41, 95%CI (1.34, 4.31)), low baseline Hb (p<0.0005, OR=3.32, 95%CI (2.52, 4.39)), PBC as treatment (p=0.017, OR=2.04, 95%CI (1.13, 3.66)) and baseline bilirubin (p=0.029, OR=1.93, 95%CI (1.07, 3.49)). Inherent sensitivity and specificity of the equation were, respectively, 77.6% and 79.2%. Conclusions: A risk predictive model for first-cycle chemotherapy-induced anaemia in patients with ST in Spain was implemented. Four predictive factors were identified. Baseline Hb values were inversely associated with toxicity. Male gender, platinum-based chemotherapy and high bilirubin values showed themselves as risk factors for anaemia. No significant financial relationships to disclose.
Diarrhea events in cancer patients (pts) treated with lapatinib
Authors: Koehler M. , Chan S. , Newstat B. O. , Preston A. , Burris H. A. 
Published: March 2020

9125 Introduction: Lapatinib (L) is an oral dual ErbB1/ErbB2 tyrosine kinase inhibitor administered to > 5,000 pts in clinical trials. Low grade gastrointestinal adverse events: diarrhea, nausea and vomiting were recorded. We characterize here the diarrhea events related to L. Methods: Diarrhea events were recorded in 1,514 pts from 8 completed MBC and non-breast cancer clinical trials. Non-L treated pts in these trials were the comparator for analysis of toxicity grades, relationship to dose, time to onset, duration, required interventions and outcomes. Results: The L dose ranged from 1,000–1,500mg daily as monotherapy (n=928) or in combination with chemotherapy (n=198). Capecitabine alone (n=191)and tamoxifen alone (n=197) pts served as controls. For L and non-L groups the per pt diarrhea rates were: any grade 50%v33%; of those G1 54%v53%; G2 30%v30%; G3 15%v17%; G4 <1%v0% and SAEs 3% v 3%; respectively. There were no fatal L-related SAEs. For L, early diarrhea presentation <6 days(d) was 2x more frequent (44%v21%). In the non-L grp, diarrhea presented at 6–14 d in 30% pts. Delayed onset (>28 d) was similar: 22% on L v 26%, non-L. Initial G3 diarrhea or progression from G1/G2 to G3 was similar (Lv non-L): 4%v 3% and 4% v3%, respectively. The median number of events/pt (2) was the same for both groups and median duration was 5d (L) v 6d (non-L). Events (L v non-L) resolved in 89%v93%; and resolved with sequelae <1% v 1%; resolution was not recorded in 7%v4%. Events were managed in approximately 30% of pts with standard anti-diarrhea medications (loperimide and lomitil) and when more sever with hydration, octreotide & antibiotics. Majority of G1/G2 events were not treated. Most pts (85%) did not have L interrupted or dose adjusted and both group only 2% (L)v 2% (non-L) discontinued therapy due to diarrhea. Conclusions: Diarrhea related to L therapy (mostly used as monotherapy in this analysis) is usually mild to moderate, frequently does not require intervention, but pts monitoring is crucial. Importantly, L-related diarrhea appears as early events (before day 6) and is generally responsive to standard interventions. Analyses are ongoing to further identify its natural history, characteristics and pts at risk for serious events. No significant financial relationships to disclose.
Relationship between performance status and malnutrition in non-selected cancer patients: A nation-wide one-day survey
Authors: Mateus C. , Cacheux W. , Lemarié E. , Michalet M. , Beauvillain de Montreuil C. , Hébuterne X. , Goldwasser F. ,   French Nutrition Oncology Study Group
Published: March 2020

9126 Background: The evaluation of the performance status (PS) is universally used in oncology and a PS of 2 is known as associated with reduced survival and increased risk of toxicity following chemotherapy. The aim of the present study was to evaluate the prevalence of malnutrition in a non selected population of cancer patients (pts) and how malnutrition correlates with poor PS. Methods: A prospective one-day prevalence survey was carried out in 154 wards of private or public hospitals in 24 cities in France. Height, present and usual body weight were assessed in outpatients and inpatients who were present that day. Malnutrition was defined as a Body Mass Index <18.5 or <21 in pts of 75 yrs or more and/or as a loss of body weight >10% from the beginning of the disease. The prevalence of malnutrition was studied in the overall population and stratified for the type of cancer and the PS. Results: 2,068 pts (1,189 men and 879 women) aged 60±13 yrs were evaluated and nutritional status was available in 1,903 pts. The PS was 0 or 1 in 52.3% of pts, 2 in 25.3%, 3 or 4 in 22.4%. Overall, 38% of pts were malnourished. Prevalence of malnutrition according to the primary tumor was: pancreas (n=42): 67%, oesophagus (n=41): 61%, stomach (n=41): 59%, head and neck (n=366): 49%, lung (n=247): 45%, ovary/uterus (n=87): 45%, colon/rectum (n=191): 39%, leukemia/lymphoma (n=377): 34%, breast (n=229): 21%, prostate (n=72): 14%. The prevalence of malnutrition was 14.4%, 31.4%, 52.3%, 53.6%, and 65.3% in pts with a PS ranging from 0 to 4, respectively. In comparison to PS-0 pts, Relative risk (RR) of malnutrition was 2.5 (p < 0.0001) in PS-1 pts and 6.4 in PS-2 pts (p<0.0001). Conclusions: Malnutrition is diagnosed in >50% of PS-2 pts. Systematic screening and care of malnutrition is mandatory to improve the PS and subsequently treatment tolerability in these pts. No significant financial relationships to disclose.
Clinical significance of CXC chemokine receptor-4 (CXCR4) and c-Met in childhood rhabdomyosarcoma (RMS) tumors
Authors: Diomedi Camassei F. , McDowell H. P. , De Ioris M. A. , Altavista P. , Cozza R. , Donfrancesco A. , Inserra A. , Callea F. , Dominici C. 
Published: March 2020

9510 Background: Both CXCR4/SDF-1 and c-Met/HGF axes promote invasive growth of RMS cells in experimental models, but no data are available on their expression and significance in RMS tumors. Expression for CXCR4 and c-Met (and their ligands) was evaluated in primary RMS tumors and correlated with clinical features, marrow involvement at diagnosis, overall (OS) and progression-free survival (PFS). Methods: Forty newly diagnosed pts, aged 2–180 months (median 58), with embryonal (n. 20) or alveolar (n. 20) RMS admitted between 1994 and 2004 were retrospectively enrolled. The only selection criterion was availability of data on marrow involvement at diagnosis as assessed by cytomorphology and immunocytochemistry for MyoD1 and myogenin. Primary site was favorable (orbit, paratesticular, uterus/vagina) in 7 pts and unfavorable (all the others) in 33. Pts were entered as group I/II (n. 5), III (n. 28) or IV (n. 7) (IRS grouping system). Marrow was infiltrated at diagnosis in 16 pts. Treatment was according to Italian RMS protocols. Expression for CXCR4, SDF-1, c-Met and HGF proteins was investigated by immunohistochemistry. Three separate counts (each >5,000 tumor cells) were performed without knowledge of clinical features and outcome; results expressed as mean percentage of immunostained tumor cells. Student t test, log-rank test, Kaplan-Meier survival analysis were applied. Institutional informed consent and ethical approval were obtained. Results: As of December 2006, median follow-up was 60 months, with 25 pts DF, 1 AWD and 14 DOD. CXCR4 and c-Met were expressed in =5% of tumor cells in all cases, but 14/40 tumors showed =50% tumor cell positivity (high expression) for either markers. High CXCR4 expression correlated with alveolar histology (p=0.006), unfavorable primary site (p=0.009), advanced group (p<0.001), marrow involvement (p=0.007), shorter OS and PFS (p<0.001). High c- Met expression with alveolar histology (p=0.005), advanced group (p=0.04), marrow involvement (p=0.02). SDF-1 and HGF were expressed by a lower percentage of tumor cells (1–95% of cells positive for the correspondent receptor). Conclusions: CXCR4/SDF-1 and c-Met/HGF pathways are clinically relevant in children with RMS and represent novel targets for disease-directed therapy. No significant financial relationships to disclose.
Ifosfamide versus cyclophosphamide: Long term gonadal effects in 166 male survivors of childhood cancer
Authors: Ridola V. , Defachelles A. S. , Schmitt C. , Fawaz O. , Gentet J. C. , Aubier F. , Michon J. , Bergeron C. , Béhar C. , Oberlin O. 
Published: March 2020

9515 Background: Alkylating agents are associated with a risk of male gonadal damage, even in patients treated during childhood. The purpose of this work was to compare this risk after treatment by ifosfamide vs cyclophosphamide during childhood. Methods: Evaluation was based on basal FSH measurement known for its correlation with spermatogenesis. LH and testosterone were also measured in most of the patients. 159 males were evaluated after treatment of a soft tissue sarcoma (79), osteoasarcoma (39), ewing (10), lymphoma (28), other (3). 100 patients received ifosfamide as unique alkylating agent and the other 59 received cyclophosphamide as the other unique alkylating agent between 1973 and 2000. Median age at treatment was 11.2 years (0–18 yrs). Median interval after the end of the treatment was 10.7 years (4.1–20.2 yrs), median age at evaluation was 21.4 years (17.5–36.1 yrs). Median dose of ifosfamide was 54 g/m2 (18- 114), median dose of cyclo was 8.3 g/m2 (4.6–22). Age at treatment and at evaluation were similar in both groups. Results: All males but two (17.5 and 26.5 yrs) had normal testosterone levels. LH was elevated in 14% of the patients. FSH was above laboratory upper limit in 28 of the 59 males (47.5%) treated with cyclophosphamide and was within the normal range in 94 of 100 patients (94%) treated with ifosfamide. Eight patients treated with cyclophosphamide fathered children. The median dose of cyclo was 5.6 g/m2 (4.8 - 10.8 g/m2). Six patients who received 51 to 54 g/m2 fathered children. The risk of abnormal FSH increased with the cumulative dose of cyclophosphamide: only 2/16 boys (12%) who received more than 12 g/m2 had a normal dosage of FSH, while 29/43 (67%) of the boys who received lower doses of cyclo did so. Conclusions: These results show a low risk of gonadal dysfunction in men exposed to ifosfamide (median dose 54 g/m2) compared to the results for males treated with cyclophosphamide. The risk of abnormal FSH increased with the cumulative dose of cyclophosphamide. No significant financial relationships to disclose.
A phase I study of clofarabine in combination with cyclophosphamide and etoposide: A new regimen in pediatric patients with refractory or relapsed acute leukemia
Authors: Hijiya N. , Franklin J. , Rytting M. , Cooper T. , Chu R. , Barry E. , McCarthy C. , Abichandani R. , Carroll W. 
Published: March 2020

9529 Background: Clofarabine is a promising new agent in the treatment of childhood leukemia as evidenced by single agent activity in previous phase I and II studies. We conducted a pilot phase I study of clofarabine used in combination with cyclophosphamide and etoposide to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT). Methods: Patients between 1 and 21 years old with relapsed or refractory acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) were enrolled. A standard 3+3 design was followed to determine the safe dose when used in combination. All drugs were administered by IV infusion daily for 5 consecutive days in induction and 4 days in consolidation. Patients received up to 2 induction cycles depending on the response, followed by consolidation cycles (maximum of 8 total cycles). The initial doses (cohort 1) were as follows: clofarabine: 20 mg/m2/day, etoposide 75 mg/m2/day and cyclophosphamide 340 mg/m2/day. Once etoposide and cyclophosphamide were escalated to their target dose (100 mg/m2/day and 440 mg/m2/day respectively in cohort 3), clofarabine was then increased to 30 mg/m2/day in cohorts 4 and would be increased to 40 mg/m2/day in cohort 5. Results: Thirteen patients (10 ALL; 3 AML) were enrolled in the first 4 dose cohorts to this date. The median number of prior regimens was 2. Response data (based on investigator assessment) are available for the first 8 patients: 6 patients (including 1 patient with AML) achieved either complete remission (CR) or complete remission without platelet recovery (CRp), for an overall response rate of 75%. Four patients proceeded to HSCT. One patient in cohort 4 experienced a DLT which resolved (grade 3 elevation of lipase) and possible veno-occlusive disease leading to cohort expansion. Common toxicities noted include febrile neutropenia and fever. Conclusions: The phase I study is ongoing until determination of MTD for this combination but these early results indicate that this combination shows significant activity in children with refractory or relapsed acute leukemias and is well-tolerated. No significant financial relationships to disclose.
A phase I study of oxaliplatin (OXA) and irinotecan (IRN) in pediatric patients with refractory solid tumors: A Children's Oncology Group study
Authors: McGregor L. M. , Spunt S. L. , Furman W. L. , Stewart C. F. , Krailo M. D. , Speights R. , Houghton P. J. , Ivy S. P. , Blaney S. M. , Adamson P. C. ,   Children's Oncology Group Phase I Consortium
Published: March 2020

9546 Background: Platinum analogues in combination with topoisomerase 1 inhibitors have been shown in in vitro studies to have synergistic anti-tumor activity. This study estimated the maximum tolerated dose (MTD) of OXA in combination with a protracted schedule of IRN in children with refractory solid tumors. Methods: OXA was administered over 2 hrs on days 1 and 8 in combination with IRN iv over 1 hr on days 1–5 and 8–12 of a 21-day cycle. An oral cephalosporin was administered daily to ameliorate IRN-associated diarrhea. Pharmacokinetic studies of OXA and UGT1A1 genotyping were performed during course 1 in consenting patients. Results: 13 patients (median age 16 yrs, 4 M) were enrolled. Dose-limiting diarrhea (n=3), serum lipase elevation (n=3), serum amylase elevation (n=2), colitis (n=1), abdominal pain (n=1) and headache (n=1) occurred at the 1st dose level (60 mg/m2/dose OXA; 20 mg/m2/dose of IRN) in the first 3 patients. Only 1/7 patients treated with reduced doses of both agents (40 mg/m2/dose OXA; 15 mg/m2/dose IRN) experienced DLT, diarrhea. When the OXA dose (60 mg/m2) was increased with the reduced IRN dose (15 mg/m2) 2/3 patients had DLT (1 diarrhea, 1 hypokalemia). Myelosuppression was minimal at all dose levels. One patient with alveolar rhabdomyosarcoma previously treated with irinotecan (dose level 2: 40 mg/m2/dose OXA; 15 mg/m2/dose IRN) had an unconfirmed complete response of her breast metastases and one patient with refractory neuroblastoma had disease stabilization through 6 courses of therapy. The frequency of 6/6, 6/7, and 7/7 UGT1A1 promoter genotypes were 5/10, 4/10, and 1/10, respectively. Conclusions: The MTD using this schedule with oral cephalosporin support was oxaliplatin 40 mg/m2/dose with irinotecan 15 mg/m2/dose. There was some evidence of benefit but significant toxicity, both expected (diarrhea) and unexpected (elevation in pancreatic enzymes), was also observed. [Table: see text]
Newly diagnosed high-risk malignant brain tumors with leptomeningeal dissemination in young children: A final update on Head Start II Regimen A2 intensified with high-dose methotrexate
Authors: Chi S. , Gardner S. , Ji L. Y. , Sposto R. , Dhall G. , Finlay J. 
Published: March 2020

9552 Background: The prognosis for young children with newly diagnosed malignant brain tumors with leptomeningeal dissemination remains poor. From Jan 1997 to Mar 2003, “Head Start II” Regimen A2, intensified with high-dose methotrexate, was offered to this high-risk population. Methods: Eligibility: patients < 10 yrs of age; confirmed diagnosis of medulloblastoma (MB), primitive neuroectodermal tumor (PNET), ependymoma and choroid plexus carcinoma (CPC); and high-risk status as determined by neuroaxis dissemination. Patients with atypical teratoid/rhabdoid tumor (ATRT), regardless of stage, were also eligible. Treatment: 5 cycles of vincristine (0.05 mg/kg/week × 3 doses), cisplatin (3.5 mg/kg), etoposide (4 mg/kg/day × 2 days), cyclophosphamide (65 mg/kg/day × 2 days), and methotrexate (400 mg/kg) with leucovorin. Children without progressive disease (PD) by the end of induction underwent a single consolidation cycle (carboplatin, etoposide, thiotepa) with autologous stem cell rescue. Reduced dose RT (2340cGy CSI and focal boost) was reserved for any with residual disease at the end of induction or for the older patient (>6 yrs of age). Results: 40 patients were enrolled (MB, 22; PNET, 6; ependymoma, 5; AT/RT, 6; CPC, 1), med age at diagnosis 38 mos (range 5 to 119 mos). Significant toxicities of this intensified regimen included GI toxicities and infections. Among the entire cohort, there were 26 CR, 6 PR, 2 with stable disease and 4 with PD (and 2 toxic deaths), for a CR +PR response rate of 82%. For disseminated MB (4 M1; 2 M2; 16 M3), the CR rate alone is 77% (17/22). The 5-year EFS and OS for disseminated MB are 45% (95% CI, 24 % to 64%) and 54% (95% CI, 31% to 72%), respectively. Of note, 6/12 MB survivors (all M3) did not receive RT and all are NED >5 years from diagnosis. In addition, there are 3 AT/RT survivors, 12, 54 and 66 mos post-diagnosis who did not receive RT. Conclusions: This intensified regimen is feasible and tolerable. For patients with disseminated MB, the majority of whom had M3 disease at diagnosis, the impressive response rate and outcomes suggest that the addition of methotrexate is justified for future studies. Long- term neuropsychological outcomes are being studied at this time. No significant financial relationships to disclose.