tbuckley/cabot-search huggingface dataset:
Randomized, phase III study of adjuvant doxorubicin plus cyclophosphamide (AC) → docetaxel (T) with or without capecitabine (X) in high-risk early breast cancer: Exploratory Ki-67 analyses.
Authors: J. E. Pippen, D. Paul, C. T. Stokoe, J. L. Blum, L. Krekow, F. A. Holmes, D. L. Lindquist, S. M. Sedlacek, R. R. Rivera, R. J. Brooks, S. J. Vukelja, K. McIntyre, C. Lopez-Diaz, J. O'Shaughnessy
Journal: Journal of Clinical Oncology (2011)

500 Background: First results of study USON 01062 comparing adjuvant AC→T vs AC→XT in high-risk EBC [O’Shaughnessy, SABCS 2010] showed the primary endpoint, improvement in DFS, was not met (median FU 5 yrs: HR 0.84, 95% CI: 0.67–1.05; p%0.125; 304 events), but a statistically significant improvement in OS was seen with AC→XT (HR 0.68, 95% CI: 0.51–0.92; p%0.011; 183 events). Given the current understanding of a lesser benefit of adjuvant chemotherapy in indolent BC, we performed unplanned exploratory subset analyses of Ki-67 expression, distant DFS and benefit from XT. Methods: Pts aged 18–70 yrs with surgically resectable EBC received 4 x 3-weekly AC (A: 60mg/m2, C: 600mg/m2, d1) → 4 x 3-weekly T (100mg/m2 d1) or XT (X: 825mg/m2 bid, d1–14; T: 75mg/m2 d1). ER+ pts received endocrine therapy, and, after 2005, HER2+ pts were offered 1-yr of trastuzumab. Primary endpoint: DFS; secondary endpoints: OS; safety. Ki-67 staining was done locally. Results: 2,611 pts were randomized: AC→T (n%1304); AC→XT (n%1307). Treatment arms were balanced. Exploratory distant DFS analysis favored the XT group (HR 0.80, 95% CI: 0.63–1.02; p%0.067). Analyses by Ki-67 expression showed a treatment effect with XT vs T in pts with Ki-67 ≥10% (HR for DFS: 0.70; OS: 0.52) (table). Very few events (DFS/OS) were seen in pts with Ki-67 <10%, with no difference in DFS with XT vs T. In pts with ER+/HER2- tumors and Ki-67 ≥10%, a trend towards DFS (HR 0.66) and OS (0.30) benefit with XT was also seen. Conclusions: Exploratory Ki-67 analyses suggested benefit of X in more highly proliferative tumors, reflecting the importance of pt selection in adjuvant trials. Pt group Pts, n AC→T events AC→XT events HR (95% CI) DFS All 2,611 164 140 0.84 (0.67–1.05) Ki-67 (All pts) <10% 326 9 12 1.34 (0.57–3.19) ≥10% 1,194 84 57 0.70 (0.50–0.98) Unknown 1,076 71 71 0.91 (0.65–1.26) Ki-67 (ER+/HER2-) <10% 273 6 9 1.47 (0.52–4.15) ≥10% 570 34 21 0.66 (0.38–1.13) Unknown 600 32 33 0.95 (0.58–1.54) OS All 2,611 108 75 0.68 (0.51–0.92) Ki-67 (All pts) <10% 326 7 5 0.72 (0.23–2.27) ≥10% 1,194 56 28 0.52 (0.33–0.82) Unknown 1,076 45 42 0.85 (0.56–1.30) Ki-67 (ER+/HER2-) <10% 273 5 4 0.79 (0.21–2.94) ≥10% 570 18 5 0.30 (0.11–0.81) Unknown 600 17 17 0.92 (0.47–1.81)
Phase II trial of paclitaxel polyglumex (PPX) with capecitabine (C) for metastatic breast cancer (MBC)
Authors: D. W. Northfelt, J. B. Allred, H. Liu, T. J. Hobday, M. W. Rodacker, A. P. Lyss, T. R. Fitch, E. A. Perez
Journal: Journal of Clinical Oncology (2008)

1063 Background: C is an established effective treatment, alone and combined with paclitaxel (P), for MBC. P causes alopecia, infusion reactions, requires corticosteroid premedication and lengthy infusion time which make therapy problematic. PPX (macromolecular conjugate of P bound to poly-L-glutamic acid) has potential advantages over P including little alopecia, short infusion time with no premedication, enhanced tumor permeability/retention effect, and estrogen-influenced metabolism which may improve tolerability and efficacy. We therefore examined tolerability and efficacy of PPX + C in patients with MBC. Methods: Single stage phase II study, interim analysis conducted with endpoints of tumor response, adverse events (AE), time to progression and overall survival. Main eligibility: age >18, no prior MBC chemotherapy, ECOG PS<2, RECIST-measurable disease, HER2-neg, no brain mets or neuropathy. Treatment: PPX 135 mg/m2 day 1 + C 825 mg/m2 BID days 1–14, 3-week cycle. 41 evaluable patients required to test null hypothesis that complete and partial tumor response rate (CR + PR) was at most 40% against the alternative of at least 60%. PPX + C would be considered promising in this population if ≥21 responses observed among first 41 evaluable patients. Results: 48 patients enrolled April 2006- April 2007; all patients evaluable. Median cycles administered = 6. 20 patients (42%; 95% CI: 28–57%) had tumor response (2 CR, 18 PR) by RECIST criteria. All 20 (49%, 95% CI: 33%-65%) responses occurred in first 41 patients, falling short of trial goal of 21. Median duration of tumor response = 11.9 months. Median follow-up = 7.6 months. Median progression-free survival = 5.7 months (95% CI: 4.2–10.0 months). 6-month overall survival = 86% (95% CI: 76–97%); progression free survival = 45% (95% CI: 32–62%). Median dose level administered = 135 mg/m2 PPX, 825 mg/m2 C for cycles 1–7. Most common severe (grade 3/4) AE: leukopenia 9 (18%), neutropenia 8 (20%), neuro-sensory 4 (9%), skin reaction-hand/foot 4 (9%), dyspnea 3 (6%). 53% (25/47) of patients experienced a grade ≥3 AE and 13% experienced a grade ≥4 AE. No alopecia was reported. Conclusions: Although the trial failed to reach goal of 21 confirmed tumor responses in the first 41 evaluable patients, PPX + C is well tolerated and active in MBC. No significant financial relationships to disclose.
Supportive care in the pregnant cancer patient
Authors: E. E. Prommer
Journal: Journal of Clinical Oncology (2005)

8254 Background: Symptom control in the pregnant cancer patient requires knowledge of which palliative care drugs are safe for the mother and the fetus. Methods: Medline search was conducted using key words, pregnancy and palliative care; pregnancy and cancer. Results: Cancer occurs in 1 per 1000 pregnancies. There have been no systematic studies of symptom prevalence in this patient population. Case reports are the main source of information regarding symptom prevalence. Key symptoms occuring in the pregnant cancer patient are pain, dyspnea, fatigue, nausea and vomiting, and anxiety. The FDA classification of drugs may be a guide to the selection of appropriate drugs for palliation. Placental transport between mother and fetus and drug excretion during breast feeding must be considered in any drug used for symptom control. Pain control can be safely achieved with opioids. Neonates must be monitored for fetal withdrawal syndrome. Pain adjuvants such as antidepressants and anticonvulsants have risk for teratogenicity and may also be excreted in breast milk. Risk/benefit must be considered for the proposed drug. Nausea and vomiting not related to pregnancy can be treated with serotonin inhibitors, butryophenones, and phenothiazines. Corticosteroids are useful palliative care agents. However, due to an increased risk of oral clefts, high doses (1–2 mg/kg) should be avoided in the first trimester. Most drugs used for depression have teratogenic risk and have potential for breast milk excretion. Paxil is not excreted in milk and buproprion has less teratogenic risk. Fatigue often requires the use of pharmacologic interventions. The teratogenicity of methylphenidate has not been characterized. Other drugs such as modafinil have teratogenic risk. Dyspnea can be treated with opioids, bronchodilators, and theophylline. Most bronchodilators have not had teratogenic risk ruled out, but terbutiline and ipatropium seem to be the safest. Treating anxiety requires careful review of the proposed agent as many of the benzodiazapines are contraindicated in pregnancy, ideally non-pharmacologic measures should be used first. Conclusions: The complexities of treating the pregnant cancer patient extend to the supportive care of these patients. No significant financial relationships to disclose.
Case-control study comparing the cisplatin-based chemotherapy toxicity between elderly (age&gt;/=70) and younger patient with lung cancer
Authors: T. Yau, S. Ashley, S. Popat, A. Norton, A. Matakidou, K. Priest, M. James, M. E. R. O’Brien
Journal: Journal of Clinical Oncology (2005)

7239 Background: Palliative chemotherapy has been proven to be an effective modality for elderly patients (age>/=70) with non-small (NSCLC) and small cell lung cancer (SCLC). However, older patients, even if fit, are often considered incapable of tolerating platinum-based systemic therapy. We therefore performed a case-control study to compare the toxicities of cisplatin-based chemotherapy between younger and elderly patient (age>/=70). Methods: : SCLC & NSCLC elderly patients (age>/=70) who received chemotherapy in Royal Marsden Hospital were matched to patient aged < 70 receiving the same chemotherapy regimen. Patients were matched based on their underlying pathology (SCLC/NSCLC), stage, performance status and treatment regimen. Toxicities outcome were assessed. Results: Between 1982–2003, 240 elderly lung cancer patients were compared with 240 younger patient. Among them, there were 117 patients with SCLC and 123 patients with NSCLC. For the haematological toxicity, elderly patients experienced more leucopenia than young patients (p=0.03). However, there was no increase in neutropenic complication (p=0.3). There was no significant difference in incidence of anaemia (p=0.3) or thrombocytopenia (p=0.4). Concerning the non-haematological toxicity, there was no significant difference in toxicities in respect to nephrotoxicity (p=0.5), neuropathy (p=0.8) or nausea/vomiting (p=0.2). Interestingly, elderly patient complained of more constipation than the young patient when they received cisplatin-based chemotherapy (p=0.05). Conclusions: We demonstrated that elderly patients tolerated the platinum-based treatment as well as younger patients. Therefore, advanced age alone should not preclude appropriate chemotherapy treatment. No significant financial relationships to disclose.
G3139 plus α-Interferon (IFN) in metastatic renal cancer (RCC): A phase II study of the California Cancer Consortium
Authors: K. A. Margolin, P. Lara, D. Quinn, J. Dutcher, P. Frankel, J. Doroshow, D. Gandara, T. Synold, S. F. Lacey
Journal: Journal of Clinical Oncology (2005)

4694 Background: Genasense (G3139) is an 18-base oligodeoxynucleotide encoding antisense for bcl-2, an anti-apoptotic protein that is upregulated in renal and other cancers. The objective of combining G3139 plus IFN in RCC was to evaluate anti-tumor activity and effects on lymphocytes. The toxicities of G3139 include fatigue, fever, myelosuppression, hepatic enzyme and metabolic abnormalities, some of which occur with IFN. Therefore, doses for each agent were less than single-agent maximum tolerated doses. Methods: Patients (pts) with RCC and ≤ 1 prior systemic treatment (Rx) (no IFN) were eligible. Other requirements: no CNS metastases, performance status 0–1, adequate organ function. Rx consisted of G3139, 7 mg/kg/day, as a continuous intravenous infusion 7 days of every 14 day cycle, plus IFN, 5 million units/m2 subcutaneously, days 4 and 6 of the first G3139 infusion, then thrice weekly. Blood for pharmacologic and immunologic correlates was collected before Rx, during G3139, and during Rx with both agents. Statistical design: Identification of a response rate ≥ 20% required ≥ 2 responses in 21 pts in first-stage accrual. Results: 23 patients were enrolled, M/F 14/9, all had nephrectomy, 17 clear cell, median age 60 (40–70) and performance status 1. The median number of Rx cycles was 3 (range 1–12). Four patients had prior systemic Rx. One pt had a partial response lasting 2.5 months. Grade 3–4 Rx toxicities were fatigue (5 pts), hypophosphatemia (5 pts), hyperglycemia (3 pts), lymphopenia (3 pts), hyponatremia (2 pts) and transaminase elevation (2 pts). Laboratory analyses of CD3+ lymphocyte apoptotic markers demonstrated no change between pre- and on-treatment levels of bcl-2 or Annexin/PI positivity by flow cytometry. Effects on cytotoxicity and pharmacokinetic analyses will be reported. Conclusions: G3139 does not appear to enhance the modest activity of IFN at the doses and schedule used in this study for advanced renal cancer. Supported by N-01-CM-17101 No significant financial relationships to disclose.
A randomized phase II open label multi-institution study of the combination of bevacizumab (B) and erlotinib (E) compared to sorafenib (S) in the first-line treatment of patients (pts) with advanced hepatocellular carcinoma (HCC).
Authors: Melanie B. Thomas, Elizabeth Garrett-Mayer, Munazza Anis, Kate Robertson Anderton, Tricia A Bentz, Andie Ray Adelman, Alan Brisendine, Vinay Duddalwar, Geoffrey R. Weiss, Abby B. Siegel, Johanna C. Bendell, Ari David Baron, Anthony B. El-Khoueiry
Journal: Journal of Clinical Oncology (2015)

337 Background: HCC is the 2 nd most common cancer worldwide. Most pts present with advanced disease and require systemic therapy. S, a multi-targeted tyrosine kinase inhibitor (TKI) is the only approved drug for HCC. B is a mAb that binds circulating ligand of the transmembrane VEGF receptor; E is a TKI that inhibits EGFR signal transduction. Published single-arm trial data suggest clinical benefit from B+E in HCC. Methods: The study was designed to estimate the HR for OS of B+E vs S with its 95% confidence interval for a sample size of 90 evaluable pts. A difference in OS favoring the B+E arm with a HR of 0.67 was expected and of interest, based on median OS for B+E and S of 15 and 11 mos. seen in previous trials.Secondary endpoints include event-free survival (EFS), toxicity, and RR. Eligible pts had advanced HCC, Childs-Pugh Class A-B7, no prior systemic therapy, preserved organ function, ECOG PS 0-2. Patients were randomized 1:1 to receive S 400 mg orally twice daily, continuously, or B 10 mg/kg IV every 14 days and E 150 mg orally daily. Treatment cycles were 28 days, restaging every 2 cycles by investigator-assessed RR per RECIST 1.1 and subsequent independent radiologic review. Results: A total of 95 pts were registered, 43 in the S arm and 47 in the B+E arm. Pts who received at least 1 dose of study drug(s) were evaluable. Data are summarized in the table. Conclusions: Based on initial data analysis, the OS of advanced HCC pts treated with B+E is consistent with that of S, and the toxicity profile and EFS of B+E compare favorably to S. Clinical trial information: NCT00881751. [Table: see text]
Locums earn more but have extra charges and fewer opportunities
Authors: Natalie G Jumper
Journal: BMJ (2017)

Iacobucci highlights a contentious but increasingly significant issue in the NHS.1 Persistent workforce shortages have created an indispensable and exploitable role for locum staff, adding further financial burden to an already stretched service. Given pay discrepancies between locum and NHS trust employees in the same role, we’re left wondering whether their value is worth the cost. …
Prevalence and predictors of second opinions from medical oncologists for early-stage breast cancer: Results from the iCanCare study.
Authors: Allison W. Kurian, Christopher Ryan Friese, Irina Bondarenko, Reshma Jagsi, Steven J. Katz
Journal: Journal of Clinical Oncology (2016)

185 Background: A second medical oncology opinion (SMO) may facilitate chemotherapy decision-making. However, little is known about the interplay between SMOs, treatment decision-making and chemotherapy use. Methods: We surveyed women newly diagnosed with early-stage invasive breast cancer and treated in 2013-2014 (response rate 70%), accrued approximately 3 months after surgery through 2 population-based SEER registries (Georgia and Los Angeles), about their experiences with medical oncologists, decision-making, and chemotherapy use. We evaluated demographic, clinical and decisional factors associated with SMO using logistic regression, and evaluated the association between SMO and chemotherapy, adjusting for clinical indication for chemotherapy, results of the 21-gene recurrence score assay, and estimated propensity for SMO given patient and tumor-specific characteristics. Results: Among 1182 insured patients who consulted any medical oncologist, 8.7% had SMO and 2.4% received chemotherapy from the SMO provider. On multivariable analysis, predictors of SMO use were younger age (odds ratio, OR 0.97 per year, 95% confidence interval, CI 0.94-0.99), education (college vs. high school graduate, OR 1.88, CI 1.06-3.33), an intermediate 21-gene recurrence score (OR 2.21, CI 1.18-4.16) and a variant of uncertain significance on BRCA1/2 gene testing (OR 5.61, CI 1.22-25.72). Satisfaction with chemotherapy decision-making was high and did not differ between patients who did vs. did not receive SMO (85.3% quite or totally satisfied vs. 86%, p-value 0.85). On multivariable analysis, chemotherapy use did not differ between SMO recipients vs. non-recipients (p-value 0.25). Conclusions: SMO use was low among early-stage breast cancer patients, and was not followed by more or less receipt of chemotherapy. High decision satisfaction regardless of SMO use suggests little unmet demand. Along with younger age and more education, the factor that predicted SMO use was uncertain results of genomic testing. Studies of precision medicine should track patients’ demand for SMO, which may rise with the dissemination of increasingly complex genomic tests. Funding: P01-CA-163233
Assessing the use of routine abdominal CT in staging evaluation of patients with primary breast cancer.
Authors: Stuart-Allison Moffat Staley
Journal: Journal of Clinical Oncology (2012)

3 Background: The purpose of this study was to determine the utility of routine abdominal CT in the staging evaluation of women with newly diagnosed primary breast cancer given no detectable disease beyond the ipsilateral axillary nodes on chest CT. Methods: The chest and abdominal CT scans from 440 patients over a 10-year period were reviewed. The presence of definite or possible metastatic disease in the axillary nodes, chest wall, internal mammary nodes, mediastinal nodes, lungs, liver and adrenals were recorded for each patient. Cross tabulation bivariate analysis as well as a chi-square test were performed to characterize the relationship between detection of disease in the chest and disease in the abdomen. Results: Of the 440 patients reviewed, the following were found to have detectable metastatic disease by CT scan: axillary nodes 258 of 440 (56.46%), chest wall 40 of 440 (9.10%), internalmammary nodes 8 of 440 (1.82%), mediastinal nodes 29 of 440 (6.59%), lung 25 of 440 (5.68%), liver 12 of 437 (2.73%), and adrenals 8 of 440 (1.82%). In total, 81 patients had disease detectable in the chest beyond the ipsilateral axillary nodes, and only 12 patients had detectable disease spread in the abdomen. Of the 359 patients who had a negative chest CT, only 1 patient had detectable or possible metastatic disease spread on abdominal CT, resulting in a 99.70% negative predictive value (p &lt; 0.001). Conclusions: The routine use of abdominal CT in women with newly diagnosed primary breast cancer and no detectable disease beyond the ipsilateral axillary nodes on staging chest CT scan has little value with a 99.70% negative predictive value. We recommend that if a negative CT scan of the patient’s chest yields no detectable disease beyond the axillary nodes, then further CT imaging of the abdomen is of no additional benefit to the patient. [Table: see text]
Impact of Different Postremission Strategies in Younger Adults with Acute Myeloid Leukemia and Normal Karyotype Exhibiting a CEBPA Mutation.
Authors: Richard F. Schlenk, Andrea Corbacioglu, Stefan Fröhling, Juan Du, Daniela Späth, Irina Schäfer, Jürgen Krauter, Arnold Ganser, Hartmut Döhner, Konstanze Döhner
Journal: Blood (2005)
Colorectal cancer screening discussions: Maybe 3As is enough?
Authors: Jennifer Elston-Lafata, Gregory Cooper, George Divine, Susan Flocke
Journal: Journal of Clinical Oncology (2012)

7 Background: We evaluate the association of the 5A steps as recommended by the US Preventive Services Task Force (i.e., assess, advise, agree, assist and arrange) with adherence to physician-recommended colorectal cancer (CRC) screening. Methods: Audio-recordings of periodic health exams (PHEs) were joined with electronic medical record data and pre-visit patient surveys. Association of the 5A steps, as coded from audio-recordings, with CRC screening use was assessed using generalized estimating equation approaches. Results: Physician participants (n=64) were salaried primary care physicians. Patient participants (n=444) were insured, aged 50-80 years and due for CRC screening. Virtually all visits (n=415) included a discussion of CRC screening. When CRC screening was discussed, patients almost always (99%) received a physician recommendation for screening (advise). Over half were given assistance in obtaining screening (assist, 59%) and told why they were eligible for screening (assess, 56%). Few negotiated a plan (agree, 16%) or discussed follow up (arrange, 3%). Just over half (56%) of patients adhered to physician screening recommendations. Multivariable model results illustrate the importance of the assess and assist steps combined (OR=1.92 [95%CI 1.03-3.57]) for patient adherence to recommended CRC screening. Other variables significantly associated with screening use included discussion of CRC screening during history taking, and decreasing patient age and body mass index. Conclusions: A relatively simple discussion at the time of a CRC screening recommendation (Advise)—one that both describes the patient’s eligibility for screening (Assess) and provides verbal help regarding how to obtain screening (Assist)—may lead to improved adherence to CRC screening.
A randomized, double-blind, placebo-controlled cross over trial of the effect on quality of life (QOL) of continuing dexamethasone beyond 24 hours following moderately emetogenic chemotherapy in women with breast cancer.
Authors: J. L. Vardy, G. R. Pond, A. Dodd, D. Warr, B. Seruga, M. J. Clemons, L. Bordeleau, I. Tannock
Journal: Journal of Clinical Oncology (2011)

9020 Background: Dexamethasone (D) improves acute nausea and vomiting when given pre chemotherapy (CTh), and continued D improves emesis after highly emetogenic CTh. There is lack of consensus about the optimal antiemetic regimen for delayed control after moderately emetogenic CTh. Many patients complain of symptoms while on D that may impact on QOL. Methods: A randomized double-blind cross-over trial compared D versus placebo (P) for delayed emesis in CTh-naïve women with breast cancer treated with moderately emetogenic CTh. All patients received IV granisetron and IV D pre-CTh and oral granisetron on day 2. Patients were randomized to oral D (4mg bid) or P for 48 hours, and changed to the alternative treatment for cycle 2. Primary endpoints were: (i) patient preference; (ii) difference between cycles in change in QOL (EORTC-QLQ-C30) from day 1 to 8. Secondary endpoints were emesis (Functional Living Index-Emesis; patient diaries) and the Dexamethasone Symptom Questionnaire. Results: Mean age of the 94 women recruited was 51yrs (range 27-76); 15 received AC and 79 FEC CTh. Thirteen women withdrew pre-cycle 2 with no difference in rates or reasons for withdrawal between arms. Thirty-one women preferred P and 37 preferred D (54% of those with a stated preference; 95% CI: 42-67%); 12 stated no preference. Of those preferring D, 54% rated it ‘much better’, compared with 39% for P. Patients had increased symptoms and decreased QOL from D1 to D8 in both cycles. There was greater decrease in global QOL (p=.06) and greater increase in pain (p=.04) when patients received D. No other symptom/QOL domains were significantly different. A non-significant decrease in vomiting intensity and delay in onset of vomiting was observed when receiving D, with no difference in nausea. Conclusions: No difference was found in patient preference, QOL or symptoms regardless of whether D or P was used for delayed emesis after moderately emetogenic CTh. We suggest continued D be omitted from initial antiemetic regimens for moderately emetogenic CTh, and offered selectively to patients with poor initial control of delayed nausea and vomiting.