tbuckley/cabot-search huggingface dataset:
Tamoxifen (TAM) for the prevention of breast cancer: Importance of specific aspects of health-related quality of life (HRQL) to global health status in the ANZ BCTG substudy of IBIS-1 (ANZ 92P1)
Authors: P. S. Grimison, A. S. Coates, J. F. Forbes, J. Cuzick, C. Furnival, P. S. Craft, R. D. Snyder, R. M. Thornton, D. F. Lindsay, R. J. Simes
Journal: Journal of Clinical Oncology (2008)

1516 Background: The International Breast Cancer Intervention Study (IBIS-1) found that 5 years of TAM compared to placebo reduced the incidence of invasive breast cancer in women at increased risk, but worsened treatment-related symptoms (Cuzick JNCI 2007). The importance of these aspects of HRQL to global health status is unclear. Methods: 729 IBIS-1 participants randomized to TAM or placebo completed the Utility Based Questionnaire-Cancer (items about 28 HRQL outcomes and global health status) at baseline, Yr 1, Yr 3 & Yr 5. Compliance with questionnaires was 99% at baseline, 92% at Yr 1, 80% at Yr 3, 60% at Yr 5. For each outcome, we compared differences between treatment groups in i) mean deterioration from baseline to each timepoint, ii) % of participants whose scores were meaningfully worse (≥ 10%) on treatment; and iii) association with global health status in multivariate analysis. Primary outcomes were vasomotor and gynecologic symptoms. Results: i) TAM was associated with greater deterioration of mean scores for hot flashes (mean change 1.5 vs 0.3 on scale from 0 to 10), vaginal discharge (0.5 vs 0.1), and menstrual problems (0.7 vs 0.1) at Yr 1 (p ≤ 0.001); and hot flashes (1.1 vs 0.5, p = 0.01), sleep disturbance, fatigue, sadness, physical and social functions (p 0.01 to 0.05) at Yr 3. ii) More participants on TAM than placebo had meaningfully worse scores on treatment for hot flashes and vaginal discharge (Table), but not global health status (26% vs 27%) or any other outcomes. iii) Changes in global health status were associated with fatigue, pain, anxiety, dyspnoea, physical and social functions (p < 0.0001); but were not influenced by changes in vasomotor and gynecologic symptoms (p > 0.1). Conclusions: TAM worsens vasomotor and gynecologic symptoms in an extra 10–12% of women over placebo. These effects do not appear to adversely affect global health status, so are unlikely to outweigh the benefits of reducing breast cancer incidence. Vasomotor and gynecologic symptoms Impairment at Baseline (%) Worse on Treatment (%) Tamoxifen Placebo p-value Hot flashes 31% 43% 31% <0.0001 Vaginal discharge 7% 19% 9% < 0.0001 Vaginal dryness 25% 21% 25% > 0.1 Menstrual problems 13% 16% 12% > 0.1 Sexual dysfunction 13% 23% 25% > 0.1 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca
Surgery for pancreatic cancer: Unnecessary or insufficient?
Authors: E. R. Witkowski, J. K. Smith, E. Ragulin-Coyne, S. C. Ng, S. A. Shah, J. F. Tseng
Journal: Journal of Clinical Oncology (2011)

e14596 Background: All potential cures for pancreatic cancer include resection. However, some patients with resectable disease do not undergo surgery, while others undergo operation but succumb quickly to recurrent disease or postoperative complications. We attempted to construct an optimal cohort of patients for resection by identifying two outlying groups who either 1) might have benefited from resection; or 2) underwent non-beneficial surgery. Methods: Patients ≥65 years old with pancreatic adenocarcinoma were identified in SEER-Medicare 1991-2007. Potential suboptimal utilization was defined as patients with locoregional disease who did not undergo resection, or patients who received resections yet died <6 months from diagnosis. Univariate and multivariate analyses were performed to identify predictors of suboptimal outcome. Survival was examined by Cox. Results: Among 17,450 patients, 9612 (55.1%) had metastases at diagnosis. For metastatic patients, 5,574 (58%) visited a surgeon, 828 (8.6%) were recommended for surgery, and 185 (1.9%) were resected. 7,604 (79.1%) of metastatic patients died within 6 months of diagnosis, including 100 (54.1%) of the highly-selected resection cohort. Younger metastatic patients were more likely to receive surgery (p=0.007). For patients with locoregional disease, only 6,001 (76.6%) visited a surgeon, 3,135 (40%) were recommended for resection, and 2,528 (32.3%) underwent operation. In locoregional disease, odds of surviving >6 months were independently increased by receipt of surgery (OR 3.9, 3.5-4.2) and chemotherapy (OR 4.9, 4.4-5.4). Resection also improved overall survival (HR 0.4, 0.38-0.42). However, of the total 2,713 all-stage resected patients, 654 (24.1%) died within 6 months of diagnosis. Conclusions: Only one-third of patients with locoregional pancreatic cancer undergo resection, suggesting potential underutilization of surgery; however, one-quarter of resected patients die within 6 months. These results suggest that surgical therapy may be imperfectly utilized in this lethal disease. Careful consideration of resection as well as more precise stratification of perioperative risk and potential for residual/recurrent disease may help optimize the cohort on whom we operate.
Preferences for oral and parenteral antitumor therapy: A survey of 260 patients with metastatic breast cancer
Authors: M. Paley, N. Love, R. Carlson, D. Tripathy, R. Kaderman, D. Paley, J. Dvorkin, K. Ziel
Journal: Journal of Clinical Oncology (2005)

619 Background: Oral, intravenous (IV), intramuscular (IM) and subcutaneous (SQ) therapies are commonly utilized to treat patients with metastatic breast cancer (PMBC), and often the risk-benefit ratios of these palliative options are similar. Two common clinical scenarios that offer choices for women with metastatic breast disease are: (1) The oral fluoropyrimidine prodrug, capecitabine or IV agents/ regimens, and (2) For postmenopausal women, daily oral endocrine agents, such as tamoxifen and aromatase inhibitors, or fulvestrant, a monthly IM injection. It is widely assumed that oral therapy is preferable, because of the perceived inconvenience and discomfort of parenteral therapy (PT). This study evaluated these preferences. Methods: PMBC were recruited to participate in an anonymous 250-item, 45-minute telephone survey focusing on a variety of issues, including preferences for oral chemotherapy (OC) vs IV chemotherapy (IC) and oral (OE) vs IM endocrine therapy (IME). Results: 260 PMBC were interviewed. Current and prior therapies included IC (88%), OC (32%), OE (84%), IME (fulvestrant: 23%), SQ endocrine therapy (12%), and IV bisphosphonates (65%). When asked to decide between two equally effective and tolerable treatments, 63% of PMBC preferred OC, 29% preferred IC and 8% were neutral. Similarly, 54% preferred OE, 36% preferred IME and 10% were neutral. Reasons for preferring PT included convenience, the belief that PT is more effective, and concerns about personal compliance with oral medications. Conclusions: Other data from this project demonstrate that medical oncologists (MO) and oncology nurses (ON) estimate that — assuming equivalent efficacy and side effects — approximately one third or more of PMBC in their practices would prefer PT. These estimates correlate with the findings in this survey. Additional data from the PMBC survey demonstrate that these patients have frequent, extended visits to the MO’s office, hold MO and ON in high regard, and value interactions with other patients during office visits. Within this context, a substantial percentage of PMBC prefers PT. These preferences should be considered when making treatment decisions with PMBC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, EMD, Onyx, Pfizer AstraZeneca, Genentech, Novartis, Pfizer, Roche Genentech, GlaxoSmithKline
Association between rigors and overall survival (OS) in metastatic renal cell carcinoma (mRCC) patients treated with high-dose interleukin-2 (HD IL-2).
Authors: Julia Anne Batten, Wolfram E. Samlowski, Kinjal Parikh, Arun Sendilnathan, Hilda Crispin, Joan Van Atta, Daniel Sageser, Kenneth F. Grossmann, Junfeng Wang, Srinivas Kiran Tantravahi, David D. Stenehjem, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2014)

487 Background: HD IL-2 is associated with an objective response rate of 16-20% with durability of response in select mRCC patients. HD IL-2 is also associated with significant toxicity including vascular leak syndrome and inflammatory side effects. Few predictive markers can identify patients likely to respond to HD IL-2. Methods: Patients treated with HD IL-2 at the University of Utah Huntsman Cancer Institute from 2000 to 2012 with clear cell mRCC were evaluated. Grade of toxicities during HD IL-2 treatment were collected based on provider documentation in the electronic health record. Rates of adverse events (AEs) and overall survival stratified grade 3 AEs were evaluated by Kaplan-Meier survival estimates and Cox proportional hazards models. All AEs were graded per common terminology criteria version 4. Grade 3 rigors were defined as severe rigors requiring opioids. Results: A total of 85 patients were included with a median age of 56 years (range 32-76 years) and 79% (n = 67) were male. Patients belonged to the following MSKCC risk categories: 11 (13%) good, 70 (82%) intermediate, and 4 (5%) poor risk. The mean total dose received was 1097 MIU (range: 160 – 3048 MIU). The prevalence of grade 3 AEs is presented in the table. Median survival of patients with ≥grade 3 rigors after HD IL-2 administration was 1501 days vs 533 days for those without (p = 0.0005, HR 2.54). Presence of rigors was also associated with a significant improvement in progression free survival, time to next treatment and response rates. No other AEs predicted response to HD IL-2. Conclusions: Presence of grade 3 rigors predicts improved survival during HD IL-2 therapy. Notably, grade 3 fever was rarely observed because of our institutional protocol of routinely using scheduled antipyretics to diminish fevers. [Table: see text]
Circulating tumor cells as a possible prognostic tool in newly diagnosed nonmetastatic colorectal cancer?
Authors: Loes Scholten, Leon W. M. M. Terstappen, Job van der Palen, Walter Mastboom, Arjan Tibbe, Istvan Vermes, Marco de Groot
Journal: Journal of Clinical Oncology (2012)

395 Background: The presence of circulating tumor cells (CTC) is associated with poor prognosis in patients with metastatic colorectal cancer (CRC). The current study was conducted to determine if the presence of CTC prior to surgery in patients with newly diagnosed non-metastatic CRC can identify those patients at risk for disease recurrence. Methods: In a prospective single center study 180 patients with newly diagnosed non-disseminated CRC scheduled for surgery were enrolled and followed up for a median of 41 months. CTC were enumerated with the CellSearch System in 4 aliquots of 7.5 ml of peripheral blood before undergoing surgery. The control group consisted of sixty patients with benign tumors after surgery or colonoscopy. Results: ≥1 CTC/ 30ml of blood were detected in 9 (15%) persons of the control group, and in 41 (23%) CRC patients. From the 180 CRC patients, 44 developed recurrent disease (24%) and 38 patients (21%) died during follow up. Presence of CTC correlated with disease recurrence (p= 0.040) and death (p=0.006). Patients with CTC had a significantly decreased three year Disease Free Survival (DFS) and overall survival (OS) versus those without CTC (DFS 57%vs. 78%, p=0.018 and OS 70% vs. 80%, p=0.003%). Conclusions: Patients with stage I-III CRC with CTC before surgery have a significantly lower 3 years DFS and OS. These findings warrant further development of technology to increased the sensitivity and specificity of CTC detection for incorporation as prognostic marker along side Duke Stage to assess which patients need adjuvant treatment.
Effect of coinfusion of dexamethasone to oxaliplatin on hypersensitivity reactions induced by oxaliplatin in patients with colorectal cancer treated with XELOX.
Authors: Naoya Aisu, Yoichiro Yoshida, Toru Miyake, Syu Tanimura, Seiichiro Hoshino, Yuichi Yamashita
Journal: Journal of Clinical Oncology (2013)

560 Background: Oxaliplatin is a third-generation platinum compound and a key agent for the management of colorectal cancer. Patients treated with oxaliplatin are at risk for hypersensitivity reactions. The incidence of severe anaphylactic reaction of oxaliplatin is estimated to be 0.5%, whereas the incidence of other hypersensitivity reactions in clinical practice is estimated to be 12% to 20%. We have reported that there is possibility that hypersensitivity reactions to oxaliplatin could have been prevented by co-infusion of dexamethasone (DEX) (Yoshida et al.2012 ASCO-GI, Yoshida et al, Br J Med Med Res 2012) but just in a small cohort. This study was undertaken to evaluate the effectiveness of co-infusion of DEX to oxaliplatin for controlling hypersensitivity reactions caused by the administration of oxaliplatin. Methods: A retrospective study of patients with advanced colorectal cancer who received XELOX was performed. The study included 101 patients who received XELOX or XELOX +bevacizumab therapy for advanced or recurrent colorectal cancer. In all the patients, oxaliplatin (130mg/m²) was administered in combination with DEX (6.6mg) via the peripheral vein. Results: A total of 101 patients were studied. Hypersensitivity reactions developed in 2 patients (1.98%).Respiratory symptoms, ocular symptoms and anaphylaxis were not observed in 101 patients. Two patients experienced cutaneous reaction (erythema). Grade 3 or higher hemotoxicity was noted in 13.9% of the patients, and grade 3 or higher nonhematological toxicity was noted in 17.8% of the patients. The response rate was 55.4%. Conclusions: Co-infusion of dexamethasone to oxaliplatin reduced oxaliplatin-related hypersensitivity reactions. This effective approach should be considered for all patients who receive XELOX, allowing treatment to be completed as planned. We have already started a new phase II trial to confirm the effects of DEX to prevent the hypersensitivity.
A phase II trial of modified triple doublets for the treatment of advanced Müllerian malignancies
Authors: U. A. Matulonis, S. Campos, C. Krasner, L. Duska, R. P. Penson, R. Falke, M. Roche, L. M. Smith, H. Lee, M. V. Seiden
Journal: Journal of Clinical Oncology (2005)

5010 Background: Previously we reported the use of three sequential doublets (Triple Doublets) in the treatment of women with newly diagnosed and advanced stage mullerian malignancies (Matulonis et al. Gyn Onc 91:293, 2003). The surgically defined negative second look operation (SLO) rate to Triple Doublets was 38%. Modifications were made to this treatment regimen to reduce toxicity and increase efficacy. Methods: Open label two-cohort study. Patients (pts) with a new diagnosis of stage II-IV mullerian malignancy were eligible. After primary cytoreductive surgery, pts were treated with 3 sequential doublets including 3 initial cycles of carboplatin (d1) and gemcitabine (day 1 and 8; doublet 1), 3 cycles of carboplatin and Taxol (doublet 2), and 3 cycles of doxorubicin (d1) and topotecan (d3,4,5; doublet 3). Cycles 1–3 and 7–9 were supported with G-CSF. After therapy, all pts were clinically staged and evaluated at SLO if clinical staging was negative for residual disease. Primary endpoints were safety and negative SLO rate with rates of 60% and 40% defined apriori as encouraging in optimally cytoreduced (cohort 1) and suboptimally cytoreduced or stage IV (cohort 2), respectively. Results: 85 eligible pts were enrolled with a median age of 52. 76, 2, and 7 women had ovarian, tubal, and primary peritoneal carcinoma respectively. 47 and 38 pts were in cohorts 1 and 2, respectively. Over 700 cycles of chemotherapy were given with no toxic deaths. Only one pt has not yet completed therapy. Grade ¾ toxicities included neutropenia in 75% of patients and thrombocytopenia in 65% of pts during at least one cycle of therapy. Fever and neutropenia were seen in 13% of pts. All grade 3 and 4 non-hematologic toxicities were seen at a frequency of <10%. 5 pts were withdrawn from trial for toxicity (2 Taxol hypersensitivity, 3 for toxicity including toxic megacolon, 2 for culmulative hematologic toxicity). 8 additional pts withdrew consent and/ or refused SLO. 70 pts underwent SLO with a negative SLO rate of 53% with an additional 9% having microscopically positive procedures. Negative SLO rate was 74% in cohort 1 and 36% in Cohort 2. Conclusions: Treatment with the modified triple doublet regimen is tolerable with an encouraging pathologic CR rate. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly, GlaxoSmithKline Eli Lilly
Phase I study of dose-escalated busulfan with fludarabine and alemtuzumab as conditioning for allogeneic hematopoetic stem cell transplantation (alloHCT)
Authors: P. H. O'Donnell, A. S. Artz, S. D. Undevia, J. Hart, K. van Besien
Journal: Journal of Clinical Oncology (2008)

7042 Background: Disease recurrence after alloHCT remains common, making improvements in conditioning regimens desirable. We hypothesized that busulfan (Bu) dose-escalation, using individualized real-time monitoring of the Bu area under the curve (AUC), might be achievable with acceptable toxicity. Methods: 37 patients (pts) (median age = 54 years, 65% male) with advanced hematologic malignancies (AML = 43%) undergoing alloHCT (matched sibling = 57%, matched unrelated = 41%) were conditioned with once-daily intravenous Bu for 4 days, plus fludarabine (Flu) and alemtuzumab. Before treatment, a 0.5 mg/kg Bu test dose was given. Bu levels after the test dose and on days 1 and 3 of conditioning allowed calculation of the AUC and clearance (Cl), and Bu doses on days 1 and 3 were adjusted to target a specified AUC. Dose level (DL) 0 was AUC = 4800 μmol-min/L/dose with a 1000 μmol-min/L/dose increase per level if < 25% of pts had dose-limiting toxicity (DLT) in the first 60 days post-HCT. Results: 36 pts were treated (8 at DL 0, 12 at DL 1, 8 at DL 2, and 8 were given a non-adjusted dose of 3.2 mg/kg/day due to technical difficulties with AUC measurements). In the cohort (n = 17) enrolled after the plasma assay was reliably standardized, Bu Cl after the test dose was significantly faster than Cl on day 1 (P = 0.001) and day 3 (P = 0.01), suggesting that test dose pharmacokinetics (PK) were not predictive of subsequent PK. Despite the absence of cyclophosphamide or post-HCT methotrexate, veno-occlusive disease (VOD) was the DLT, occurring in 0 pts at DL 0, 1 pt at DL 1, and 5 pts at DL 2 (6800 μmol-min/L). Two pts receiving the 3.2 mg/kg/day dose exhibited VOD. VOD was significantly more common in pts with a higher Bu day 1 AUC, a higher day 1+3 average AUC, and a higher peak AUC (P < 0.04). VOD was uniformly of late onset (median = 52 days, range = 33–77 days). Conclusions: Bu dose-escalation using real-time AUC monitoring is achievable, but Cl of a test dose is faster than, and not reliably predictive of subsequent treatment dose PK. Delayed VOD occurs frequently and is related to Bu AUC in pts receiving Bu/Flu/alemtuzumab conditioning. A phase II trial incorporating individualized Bu dosing to achieve a maximum-tolerated AUC of 5800 μmol-min/L/dose is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Protein Design Labs
Outcome of hypofractionated biological optimized dose-painting radiotherapy for high-risk prostate cancer.
Authors: Isabel Syndikus, Eva Onjukka, Julien Uzan, Alan Nahum
Journal: Journal of Clinical Oncology (2015)

107 Background: Prostate dose-painting radiotherapy and hypo-fractionation both can improve biochemical contol in localised disease. We report toxicity and outcome for a cohort of high risk patients. Methods: We selected 28 patients with high-risk localised prostate cancer and 2 or 3 risk factors. Functional MRI’s were used to define boost volumes with a margin of 5 mm PTV. Neo-adjuvant hormone therapy was given for 3 months. Dose volume constraints, TCP and NTCP parameters were used for optimization of rotational IMRT treatment plans. We used fiducial markers, bowel and bladder preparation and daily IGRT. Results: Mean age was 66 years, mean PSA was 17.4 ng/ml (range 4.6-59.1), 20 patients had T3a and 10 had Gleason score ≥ 8. The mean dose to the prostate excluding the boost volume was 61.4 Gy (range 60.6-62.3) and the boost PTV 66.1 Gy (range 60.9-72.5). Mean NTCP for rectal bleeding was 4.7% (range 3.4-5.8), for faecal incontinence 3.5% (range 2.3-5) and mean TCP 75% (range 71-79) assuming a 71% biochemical control at 5 years for a standard plan. All patients completed radiotherapy, 16/28 patients had acute bladder toxicity grade 2 (RTOG score), but no grade 3 toxicity was observed. Worst acute bowel toxicity was grade 1 (4/28). Mean follow up was 15 months (range 8-25). For the 20 patients who had neo-adjuvant hormone therapy beyond 6months, the mean PSA was 0.33 ng/ml (range 0.2-0.8), 2 patients had relapsed at 12 month, 6 patients are still on hormone therapy. 4 patients had Grade 2 urinary late toxicities (CTCv4). Two patients developed grade 1 diarrhoea. Patient reported outcomes &gt;6 month after completion of radiotherapy (EPIC QOL questionnaire) demonstrated similar scores to controls without prostate cancer for the bowel domains; reduction in the urinary domains was similar to other cohorts treated with external beam radiotherapy and hormone therapy. Conclusions: In this high risk group, dose escalation with hypo-fractionated dose painting radiotherapy achieved good biochemical control and urinary and bowel toxicity similar to standard dose radiotherapy during follow up.