tbuckley/cabot-search huggingface dataset:
Multicenter review of fertility preservation and contraceptive information provided to cancer patients.
Authors: A. G. Murphy, R. Roberts-Thomson, G. O'Sullivan-Coyne, M. Crowley, B. Bystricky, E. Moylan, S. O'Reilly
Journal: Journal of Clinical Oncology (2010)

e19640 Background: Cancer treatments can adversely affect fertility. Guidelines are available to help physicians both in approaching this topic and in making recommendations as fertility preservation options are constantly developing. Patients desire information on how treatments affect fertility. Assessing patients' awareness of these issues is necessary to guide future discussions with patients being treated with cytotoxic agents. Methods: An anonymous survey of patients, 50 years or less, having chemotherapy in 3 institutions in Cork, Ireland (population 400,000) was undertaken with prior ethics approval. We aimed to assess if fertility issues had been addressed prior to chemotherapy administration and if the patient was satisfied with the discussion. We also examined the degree of patient concern about fertility issues, the utilization of contraception and fertility preserving methods and patient perception of their efficacy. Results: Forty-eight patients participated; mean age 36.5 years (standard deviation: 9.6 years). Thirty-nine patients were female (81%). Half of the patients (24/48) had breast cancer and 79% (38/48) had a primary tumor. Most patients were single (41.6%) and 56.3% already had children. Of those surveyed, 31.3% wanted or strongly wanted more children (27% were unsure). A majority (77%) reported that their doctor had discussed fertility issues and these patients were more likely to feel that their concerns had been addressed (p<0.0001). Younger patients were more likely to have discussed fertility issues (p=0.0095). Only 18.8% (9/48) of patients were using contraception. Those using contraception were more likely to have discussed fertility issues with their doctor (p=0.05). If fertility issues were discussed, so too were contraception and the ability to have children (p<0.0005). Some patients (10.4%) were unaware that chemotherapy can affect fertility and many were unsure (39.6%). No associations were seen between fertility discussion and cancer type, stage, marital status or gender. Conclusions: It is important that fertility and contraceptive issues are raised in patients having chemotherapy in order to address concerns and influence contraceptive practices. No significant financial relationships to disclose.
Association of primary melanoma ulceration and clinical benefit of adjuvant vaccination with tumor-specific antigenic peptides
Authors: J. Baurain, M. Stas, F. Hammouch, A. Gillain, A. Feyens, N. Van Baren, I. Tromme, R. Van Wijck, M. Garmyn, P. G. Coulie
Journal: Journal of Clinical Oncology (2009)

3022 Background: Therapeutic vaccination of metastatic melanoma patients with detectable disease is followed by tumor regression in ±10% of the patients, mostly with locoregional disease. Considering the absence of an effective treatment to prevent relapses of cutaneous melanoma, we have applied a multipeptide vaccine in the adjuvant setting. Methods and Results: We treated 45 HLA-A2-positive melanoma patients with no evidence of disease but at high risk of relapse. They received 5 vaccines every 3 weeks, then one every 3 months over 2 years. A first group (n=14) received 4 antigenic peptides derived from MAGE-A3, NA17, gp100 and Tyrosinase, emulsified independently in 4x1ml of Montanide ISA51. A second group (n=16) received the 4 peptides emulsified together in 1x1ml of Montanide. A third group (n= 15) received the 4 peptides alone. Forty-one patients were eligible for immune response analysis after 5 injections. A T-cell response to at least one peptide was detected in 21/27 patients vaccinated with Montanide, but in none of 14 vaccinated with peptides alone. Median follow-up time was 24 months ±10 months (SD). Relapse free survival (RFS) at 18 months was 37% for all the patients and no significant difference was observed between patients vaccinated with or without Montanide: 41% and 27%, respectively. Median distant metastasis-free survival time (DMFS) was doubled for patients vaccinated with vs without Montanide (p=0.132). Multivariate analysis for various prognostic factors including sex, age, PS, vaccine type, or immune response suggested that the ulceration of the primary tumor was associated with a better clinical course following vaccination (HR=0.295 with IC95%: 0.09–0.97). Conclusions: Vaccination with mutiple peptides in Montanide is well tolerated and elicits specific immune responses. Patients vaccinated with peptides in Montanide have a prolonged RFS and DMFS compared to whose vaccinated with peptides alone. Patients who had an ulcerated primary tumor seem to benefit more from this adjuvant vaccine. These results warrant further evaluation of such vaccines in a randomized trial with the ulceration of the primary tumor as a stratification factor. No significant financial relationships to disclose.
Use of elevated baseline IL-8, CCL-2, and TNFα to predict for shorter overall survival (OS) in men with metastatic prostate cancer initiating androgen-deprivation therapy (ADT).
Authors: Jaya Sharma, Kathryn P. Gray, Mari Nakabayashi, Gillian Petrozziello, Carolyn Evan, Raina Fichorova, Philip W. Kantoff, Christopher Sweeney
Journal: Journal of Clinical Oncology (2012)

13 Background: Inflammation associated chemokines and cytokines have been shown in preclinical models to lead to the induction of castration resistance. We assessed whether higher blood cytokines and chemokines were associated with shorter time to CRPC and OS in patients initiating ADT for metastatic prostate cancer. Methods: A retrospective analysis of inflammatory markers including IL1β, IL-6, IL-8, TNFα and CCL-2 was undertaken in men initiating ADT for metastatic prostate cancer. Proteins were measured using multiplex electrochemiluminescence assays. The analytical cohort of 122 patients included a prospective trial (50 patients) and chart review (72 patients). A multivariate COX model was used to investigate the relationship between serum markers of inflammation and time to CRPC and OS. The covariates were age at time of ADT, ECOG score, race, baseline PSA, and extent of disease. Results: At time of initiating ADT, the median age of the cohort was 67 years, median PSA was 27.4, 82% had an ECOG PS of 0, 62% had extensive metastatic disease and 91% were Caucasian. Median OS was 42.2 months. The median (med) baseline levels for IL8 was 9.3pg/ml, TNFα was 2.4 pg/ml and CCL-2 was 507.5 pg/ml. As detailed below, patients with elevated IL-8, TNFα and CCL-2 had a significantly shorter OS and showed a non-significant shorter time to CRPC. Conclusions: In men with metastatic prostate cancer starting ADT, higher serum inflammatory markers are associated with poorer OS. This correlative data suggests that anti-inflammatory strategies which improved ADT efficacy in preclinical models may be relevant to the clinical setting. [Table: see text]
Neoadjuvant cisplatin (CDDP) chemotherapy (CT) with docetaxel (D) and cetuximab (Cmab) followed by concurrent radiochemotherapy (RTCT) in locally advanced head and neck cancer (LA-HNC).
Authors: P. G. Tsoutsou, M. Panteliadou, E. Papadopoulou, I. Abatzoglou, K. Sismanidou, M. Tsiarkatzi, M. I. Koukourakis
Journal: Journal of Clinical Oncology (2010)

e16025 Background: Induction CT with D and CDDP followed by concurrent platinum RTCT has emerged as a therapeutic option for LA-HNC. Cmab also challenged the role of CDPP in RTCT. A schedule based on these advances may be valuable in the treatment of LA-HNC. Methods: Patients (pts) with LA-HNC are included in a pilot phase I-II study, having as primary endpoint tolerance and as secondary local progression-free (LPFS), distant metastasis-free (DMFS) and overall survival (OS). Thirteen pts (median age 68 years, median PS 0) with LA-HNC participated. A short course of neoadjuvant CT (two bi-weekly cycles) with D (40mg/m2), CDDP (60mg/m2) and Cmab (400mg/m2) was applied before RTCT with weekly CDDP (40mg/m2) and Cmab (250 mg/m2). Conformal RT was given in 19-21 daily fractions of 2.7Gy supported with high- dose daily amifostine (500-1000mg, using a previously described algorithm). After completion, the same induction regimen was given for 2-4 cycles, depending upon tumor response. The study has completed accrual. Results: Analysis of a minimum of 7 months (m) of follow-up (FU) is presented. Induction CT was well tolerated with only 1 pt experiencing grade (G) 3 leucopenia, 1 pt with G3 anemia and no pt experiencing any thrombopenia. Fatigue of G2 in 3 pts and G3 in 1 pt was noted. Cetuximab was well tolerated with 5 pts experiencing G2 rash and 1 G3. Concurrent RTCT was also well tolerated: 7 pts presented with G1/2 and 1 with G3 mucositis and 1 pt with G1 fungal infection. Amifostine was well tolerated and no pt had any rash. Cetuximab-related rash did not deteriorate during RT. No other toxicities were noted. Minimal/partial response to CT was noted in 11/13 pts. Complete response to RTCT was noted to 11/13 pts. Median LPFS was 9.07m (range: 7-18), with 4 pts experiencing a local recurrence, DMFS was 9.53 m (7-18) with 2 pts having a distant metastasis and OS was 9.61m with all pts alive at the time of the evaluation. Conclusions: The above regimen appears safe and effective for LA-HNC. Although this interim analysis provided no superior results to a previous published study of ours using the RTCT regimen alone, a phase II study is ongoing to extract mature results. No significant financial relationships to disclose.
The biomarker serum S100B identifies responders and prolonged survival in stage IV melanoma
Authors: B. De Gast, L. Smit, J. Haanen, H. Bonfrer
Journal: Journal of Clinical Oncology (2004)

7519 Background: Previously we reported the value of serum S100B in stage III B/C melanoma. Increased values (≥0.16 μg/l) probably reflect actual hematogenous dissemination and are correlated with early (in 1st year) distant metastasis and decreased survival compared to patients with normal S100B values. We subsequently studied prospectively the value of serum S100B in stage IV melanoma. Methods: In a large series of patients (n=145) treated with chemotherapy (Temozolomide), serum S100B was determined at start, following 2 cycles of chemotherapy and in regular follow-up (1–4 years). Results: Normal serum S100B (< 0.16 μg/l) was found in 33/145 (23%) patients at start. Follow-up showed that 29/33 developed an increased S100B after a median of 7 months. The 4 exceptions had either durable CR (n=2) or were lost to follow-up after 3 and 7 months. The group was characterized by a high response rate (15/33 = 45%, 3 CR), presence of only 1 or 2 metastatic sites (85%), mostly soft tissue or lung metastases (30 and 33%) and prolonged survival (median 14m). In addition patients with slightly elevated S100B (0.16–050 μg/l) but rapid normalization on chemotherapy (n=14) had a high response rate (11/14 = 79%, 5 CR), 1–2 metastatic sites (95%) and prolonged survival (median 17 m). Patients with normal or normalized S100B following 2 cycles of chemotherapy (n=41) had a prolonged survival (15.4 months) and 20% achieved a durable remission. The other patients (n=104) had a significantly shorter survival (6.6 months, p=0.001) and none of them achieved a durable remission. Conclusions: A stably normal or rapidly normalizing S100B identifies a patient group in stage IV melanoma with limited and favorable metastatic sites and prolonged survival. These patients might benefit from intensive multi-modality treatment consisting of chemotherapy followed by surgery of (residual) metastases and immunotherapy to achieve durable CR. Normal S100B in stage IV is not genetically determined and distant (microscopic) metastasis probably occurred in an earlier stage of the disease (e.g., stage IIC, III B/C) prior to surgery. Serum S100B should be used as a stratification factor in future trials of stage IV melanoma. No significant financial relationships to disclose.
Phase Ib study of the safety, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of the humanized monoclonal antibody (huMAb) anti-EGFL7 (MEGF0444A) in combination with bevacizumab (bev) with or without paclitaxel.
Authors: Jonathan Wade Goldman, Michael S. Gordon, Pamela N. Munster, Emily K. Bergsland, Amy Patricia Moore, Shuang Bai, Priti Hegde, Jill O. Fredrickson, Ilsung Chang, G. Scott Chandler, Roel Peter Funke, Ina Park Rhee, Daniel S. Chen, Lee S. Rosen
Journal: Journal of Clinical Oncology (2012)

e13000 Background: Epidermal growth factor-like domain 7 (EGFL7), is a vascular-restricted, tumor selective, extracellular matrix protein that forms peri-vascular tracks and promotes endothelial cell adhesion and survival. These activities are inhibited by the huMAb anti-EGFL7 (MEGF0444A), which significantly enhances the efficacy of anti-VEGF in murine tumor models. A Phase Ia dose escalation of single agent MEGF0444A demonstrated no dose-limiting toxicities (DLTs). Methods: A standard 3+3 dose escalation design was used to study safety, PK, PD, and anti-tumor activity of MEGF0444A in a 2-arm Phase Ib trial in patients (pts) with advanced solid tumors. In Arm A, 22 pts received MEGF0444A at doses of 2, 5, or 10 mg/kg with bev 10 mg/kg q2w. In Arm B, 18 pts additionally received paclitaxel 90 mg/m 2 weekly. Subsequent Arm A expansion cohorts have examined flat dosing of MEGF0444A (600 mg) as a rapid infusion, serial tumor biopsies, and pts with renal cell carcinoma (RCC), respectively. Circulating progenitor cells (CPCs) and dynamic contrast enhanced MRI (DCE-MRI) were assessed as PD biomarkers. Results: The combination of MEGF0444A and bev with or without paclitaxel was well-tolerated without DLTs, exacerbation of bev-related adverse events (AEs), or AEs attributed to rapid infusion. MEGF0444A demonstrated linear PK, and flat dosing yielded MEGF0444A exposures similar to those predicted using Phase Ia weight-based dosing data. CPCs decreased in a subset of pts at the 5 mg/kg q2w dose. DCE-MRI showed a trend toward decreased K trans at this dose, supporting combination activity with bev. Eight partial responses, 2 in Arm A and 6 in Arm B, were observed across multiple tumor types. Conclusions: MEGF0444A has demonstrated safety, favorable PK, and clinical activity in combination with bev and bev/paclitaxel. PD biomarker modulation supports a recommended Phase II dose equivalent to 5 mg/kg q2w. RCC and tumor biopsy cohorts remain active. Randomized Phase II trials of MEGF0444A in combination with chemotherapy and bev in colorectal cancer and non-small cell lung cancer are underway.
Ethnicity is associated with recurrence in patients with resected gastric cancer
Authors: H. Husain, G. Lurje, D. Yang, W. Zhang, A. E. Hendifar, S. Ashouri, A. Pohl, P. C. Manegold, S. Iqbal, A. B. El- Khoueiry, H. J. Lenz
Journal: Journal of Clinical Oncology (2008)

15511 Background: Previous studies suggest that there are differences in survival among Asian and Caucasian patients with gastric cancer. It remains unclear whether disparities of treatment, differences in staging, or individual tumor biology account for this effect. The present study examines differences among ethnicities in time to tumor recurrence (TTR) in patients with resected gastric cancer. Polymorphisms in thrombin-receptor 1 (PAR1), endostatin (ES), and interleukin 8 (IL-8) are important in angiogenesis and have been implicated in gastric cancer recurrence. We tested whether the frequency of these polymorphisms provide a molecular basis for differences in TTR in different ethnic groups. Methods: Between 1992 and 2007, 105 patients (41 females and 64 males with a median age of 57 yrs; range = 26–85) with gastric adenocarcinoma underwent gastrectomy at the University of Southern California. There were 36 Caucasian, 1 African American, 24 Asian, and 44 Hispanic patients. The median follow-up was 2.4 years (range = 0.1–12.3). 47 of 105 patients (45%) developed tumor recurrence with a 5-year probability of 0.38 ± 0.06. We determined allelic frequencies of PAR1, ES, and IL-8 using PCR-RFLP. Results: Time to recurrence was significantly different by ethnic background (p=0.021, log-rank test). The median TTR for Asians was 7.0 yrs, for Hispanics was 3.7 yrs, and for Caucasians was 1.7 yrs. Gastroesophageal (GE) junction tumors had a shorter TTR compared to other tumor locations (2.1 yrs vs. 3.1 yrs, p=0.021). Allelic frequencies in genes for PAR1 and ES were statistically different between Asians, Hispanics, and Caucasians (PAR1 p=0.008; ES p=0.05), but there were no statistical differences for IL-8. Multivariate analyses including sex and age showed that ethnicity remained significant predicting TTR. Conclusion: Our study demonstrates significant differences in time to recurrence after gastrectomy favoring Asians and Hispanics. Genes in PAR1 and endostatin may provide a molecular basis for differences in TTR and may suggest different biologies of cancer between Caucasian, Hispanic, and Asian populations. Further studies are warranted to characterize molecular markers comparing different ethnic groups with resectable gastric cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, Genentech™ BioOncology, ImClone Systems Incorporated, Merck, Pfizer Oncology, Response Genetics Genentech™ BioOncology, Merck, Pfizer Oncology, Roche, sanofi-aventis NIH
Alemtuzumab in clinical practice: A British Columbia experience
Authors: D. Hui, W. Lam, C. Toze, M. Delorme, M. Noble, P. Klimo, J. Sutherland, K. Gill, J. Connors, L. Sehn
Journal: Journal of Clinical Oncology (2007)

8098 Background: Limited information is available on alemtuzumab in the non-clinical trial setting. We evaluated its efficacy and safety in 42 consecutive unselected patients who received alemtuzumab monotherapy in British Columbia between October 2002 and August 2006. Methods: Information on patient demographics, baseline clinical and pathologic characteristics, dose and schedule of treatment, clinical response, survival, and toxicities associated with alemtuzumab were collected retrospectively. Results: Thirty-nine of 42 patients had chronic lymphocytic leukemia, 2 had mycosis fungoides, and 1 had T-cell post-transplant lymphoproliferative disorder. In contrast to previous reports, 42% were treated by community practitioners and 83% received alemtuzumab subcutaneously. The median time from diagnosis to alemtuzumab was 58 months, with a median age of 63 years at alemtuzumab treatment. Patients received a median of 4 treatments prior to starting alemtuzumab. One of 42 patients (2%) achieved a complete response, 20 (48%) achieved a partial response, 13 (31%) had stable disease, and 4 (10%) had progressive disease. The median post-alemtuzumab overall survival was 15.1 months and the median progression-free survival was 5.4 months. Response to alemtuzumab correlated with an increased progression- free survival (11 months versus 3.6 months, p=0.001) and time to next treatment (15.7 months versus 5.4 months, p=0.004). Significant adverse events included grade 3 or 4 neutropenia (75%) or thrombocytopenia (42%), infections (54%) including CMV reactivation (6%), and death (12%). Patients who received alemtuzumab in the community setting had a higher incidence of febrile neutropenia (p=0.05) and infection (p=0.03) compared to academic centres, although no difference in overall survival was noted. Conclusion: Alemtuzumab can be safely administered in a wide variety of clinical settings, including community practice, and is associated with a high level of activity. No significant financial relationships to disclose.
SPARE: A qualitative study investigating randomization barriers in a Selective Bladder Preservation trial (SBP) (ISCRCTN: 61126465)
Authors: C. Moynihan, E. Hall, R. Lewis, A. Birtle, G. M. Mead, R. Huddart
Journal: Journal of Clinical Oncology (2009)

5077 Background: Recruitment to randomised trials is challenging, especially when treatment strategies are complex. While studies have demonstrated barriers to recruitment, few have investigated why patients accept or refuse randomisation. The SPARE feasibility study included such an investigation to highlight difficulties that might be dealt with as the study progressed and to inform procedures for a subsequent phase III trial. Methods: Patients had newly diagnosed invasive bladder cancer and were receiving neoadjuvant chemotherapy prior to invitation to a randomised trial (SPARE) that offered the possibility of radical cystectomy or SBP. Patients allocated SBP received cystectomy or radiotherapy dependent on chemotherapy response. 15 acceptors and 10 decliners to randomisation participated in the qualitative substudy. Methods included recorded transcribed interviews and a ‘framework analysis.’ Results: Both groups experienced initial confusion, ‘muddled’ communication, information overload, and lack of time leading to misunderstandings about the trial. Perceived side effects did not necessarily inform decisions. Decision to participate was seldom made unilaterally. Individual specialist input by, and continuity between, professionals and their patients, appeared to make decision making easier. Acceptors were inclined to altruism and trust in the medical profession, often agreeing to participate with minimum understanding regarding randomisation and/or equipoise and a ‘nothing to lose’ attitude as long as withdrawal from the trial was possible. Decliners tended to opt for radiotherapy, perceived as a rational choice in the context of this trial; many abhorred the thought of surgery that was perceived as undermining and a ‘treatment in reserve.’ Conclusions: Health professionals need to consider streamlining procedures and recognise patient preferences in terms of treatments offered and information received. Recognition of the complexity of communicating equipoise and randomisation may increase ‘informed consent’ levels and recruitment rates. A further qualitative substudy investigating doctor/patient consultations in real time with confidential feedback is proposed to optimise recruitment rates. No significant financial relationships to disclose.