Pemetrexed in combination with cisplatin versus cisplatin monotherapy in E ast A sian patients with recurrent or metastatic head and neck cancer: Results of an exploratory subgroup analysis of a phase III trial

Aim: An exploratory subgroup analysis of E ast A sian ( EA ) patients in a phase III trial was conducted to assess efficacy and safety trends based on ethnicity. Methods: The 795 patients with recurrent or metastatic squamous cell carcinoma of the head and neck included 111 EA patients randomized to pemetrexed‐cisplatin ( n  = 55) and placebo‐cisplatin ( n  = 56) and 684 non‐ EA patients randomized to pemetrexed‐cisplatin ( n  = 343) and placebo‐cisplatin ( n  = 341). Treatment differences in median overall survival and progression‐free survival were compared using a stratified log–rank test. Survival was estimated using the K aplan– M eier method. Results: The median overall survival in the pemetrexed‐cisplatin and placebo‐cisplatin arms of the EA group (6.8 and 5.7 months, respectively [ P  = 0.275]) was similar to that in the global population (7.3 and 6.3 months, respectively [ P  = 0.082]); the median progression‐free survival in the pemetrexed‐cisplatin and placebo‐cisplatin arms in the EA group (2.8 and 1.9 months, respectively [ P  = 0.748]) was similar to that in the global population (3.6 and 2.8 months, respectively [ P  = 0.166]). Compared to the findings in the global population, overall survival for the EA group receiving prior platinum‐based therapy was longer ( P  = 0.042 vs P  = 0.065). There was no significant interaction between treatment arms and ethnicity. Conclusion: Consistent with findings in the global population, pemetrexed‐cisplatin did not improve survival compared with placebo‐cisplatin for the EA group . However, in a subgroup analysis, pemetrexed‐cisplatin showed an overall survival advantage in EA patients receiving prior platinum‐based therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101808/1/ajco12060.pd

Phase II Trial of Docetaxel Chemotherapy in Patients with Incurable Adenocarcinoma of the Esophagus

Background : Chemotherapy remains theprimary mode of treatment for metastaticcarcinoma of the esophagus. The efficacyof various chemotherapeutic regimens hasbeen studied predominantly in patients withsquamous cell carcinoma of the esophagus. In light of the increasing incidence ofadenocarcinoma of the esophagus, studiesevaluating newer chemotherapy agents, suchas docetaxel, in this patient populationare necessary. The objective of this trialwas to determine the complete and partialresponse rate of docetaxel in patients withincurable adenocarcinoma of theesophagus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45210/1/10637_2004_Article_390685.pd

Classification of TP53 mutations and HPV predict survival in advanced larynx cancer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134126/1/lary25915-sup-0001-suppinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134126/2/lary25915_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134126/3/lary25915.pd

Manual Scalp Cooling in Early Stage Breast Cancer: Value of Caretaker Training and Patient-Reported Experience to Optimize Efficacy and Patient Selection

Title: Manual scalp cooling in early stage breast cancer: value of caretaker training and patient-reported experience to optimize efficacy and patient selection Authors: Manaz Rezayee1, BS Nicole Moxon1, RN Staci Mellinger1, RN Amanda Y. Seino1 Nicole E. Fredrich1 Tracy L. Kelly1 Susan Mulligan2, MA Patrick Rossi3, MD Ijeoma Uche1, MD Walter J. Urba1, MD PHD Alison K. Conlin1, MD MPH Janet Ruzich1, DO David B. Page1, MD Background: Alopecia is an emotionally distressing common adverse effect of curative-intent chemotherapy in early stage breast cancer.1–6 Although machine-based scalp cooling is effective for reduction of chemotherapy-associated alopecia in early stage breast cancer, availability is geographically limited.7–11 Manual cold-cap systems may also be effective and are available regardless of geographic location.12–14 We evaluated the feasibility of caretaker-administered cold-cap efficacy following structured standardized training, and utilized patient-reported subjective outcomes to develop a clinical tool to facilitate patient selection. Patients and Methods: A small pilot study (n=10) was conducted to evaluate the feasibility and efficacy of manual cold capping. Key eligibility criteria included: 1) no hair loss at baseline; 2) no pre-existing scalp condition; 3) planned curative-intent chemotherapy for early stage breast cancer and 4) availability of caretaker(s). Participants received standardized training and then performed the cold-cap procedure without assistance. The primary endpoint was post-treatment hair retention using Dean’s alopecia scale, with success defined as Results: Of the evaluable patients, 80% (n=8/10) met the primary efficacy endpoint (Dean’s scale 0-2) with 20% (n=2/10) trial failures due to pre-mature discontinuation. Manual cold-capping was worthwhile to 90% of patients (Was it Worth It? Questionnaire) and associated with favorable PROs. Patient interviews identified a number of themes shared by almost all patients, which were subsequently used to develop a questionnaire to aid patient-directed decision-making on whether to pursue manual cold-capping. Conclusion: This study affirms the safety and efficacy of manual cold-capping to reduce alopecia and demonstrates the importance of proper training and education to maximize efficacy. It also highlights the considerable costs and effort associated with cold-capping. Selected patients with early stage breast cancer may benefit subjectively from cold capping while the proposed clinical instrument can be used to facilitate an informed discussion between patient and provider.https://digitalcommons.psjhealth.org/cancer_institute_fellowships/1000/thumbnail.jp

A Phase II Biomarker-Embedded Study of Lapatinib plus Capecitabine as First-line Therapy in Patients with Advanced or Metastatic Gastric Cancer

Abstract An exploratory phase II biomarker-embedded trial (LPT109747; NCT00526669) designed to determine the association of lapatinib-induced fluoropyrimidine gene changes with efficacy of lapatinib plus capecitabine as first-line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma independent of tumor HER2 status. Tumor biopsies obtained before and after 7-day lapatinib (1,250 mg) to analyze changes in gene expression, followed by a 14-day course of capecitabine (1,000 mg/m2 twice daily, 14/21 days) plus lapatinib 1,250 mg daily. Blood samples were acquired for pharmacokinetic analysis. Primary clinical objectives were response rate (RR) and 5-month progression-free survival (PFS). Secondary objectives were overall survival (OS), PFS, time to response, duration of response, toxicity, and identification of associations between lapatinib pharmacokinetics and biomarker endpoints. Primary biomarker objectives were modulation of 5-FU-pathway genes by lapatinib, effects of germline SNPs on treatment outcome, and trough steady-state plasma lapatinib concentrations. Sixty-eight patients were enrolled; (75% gastric cancer, 25% gastroesophageal junction). Twelve patients (17.9%) had confirmed partial response, 31 (46.3%) had stable disease, and 16 (23.9%) had progressive disease. Median PFS and OS were 3.3 and 6.3 months, respectively. Frequent adverse events included diarrhea (45%), decreased appetite (39%), nausea (36%), and fatigue (36%). Lapatinib induced no changes in gene expression from baseline and no significant associations were found for SNPs analyzed. Elevated baseline HER3 mRNA expression was associated with a higher RR (33% vs. 0%; P = 0.008). Lapatinib plus capecitabine was well tolerated, demonstrating modest antitumor activity in patients with advanced gastric cancer. The association of elevated HER3 and RR warrants further investigation as an important player for HER-targeted regimens in combination with capecitabine. Mol Cancer Ther; 15(9); 2251–8. ©2016 AACR.</jats:p

Chemotherapy alone for organ preservation in advanced laryngeal cancer

Background. For patients with advanced laryngeal cancer, a trial was designed to determine if chemotherapy alone, in patients achieving a complete histologic complete response after a single neoadjuvant cycle, was an effective treatment with less morbidity than concurrent chemoradiotherapy. Methods. Thirty-two patients with advanced laryngeal or hypopharyngeal cancer received 1 cycle of induction chemotherapy, and subsequent treatment was decided based on response. Results. A histologic complete response was achieved in 4 patients and were treated with chemotherapy alone. All 4 patients' cancer relapsed in the neck and required surgery and postoperative radiotherapy (RT). Twenty-five patients were treated with concomitant chemoradiation. Three patients were treated with surgery. Overall survival and disease-specific survival at 3 years were 68% and 78%, respectively. Conclusion. Chemotherapy alone is not feasible for long-term control of regional disease in patients with advanced laryngeal cancer even when they achieve a histologic complete response at the primary site. © 2009 Wiley Periodicals, Inc. Head Neck, 2010Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77508/1/21285_ftp.pd

Multicenter phase II trial of brequinar sodium in patients with advanced squamous-cell carcinoma of the head and neck

A total of 19 patients with advanced squamous-cell carcinoma of the head and neck who had not previously been exposed to chemotherapy were treated with brequinar sodium as first-line chemotherapy. Brequinar was given intravenously at a median weekly dose of 1,200 mg/m 2 . The toxicity was moderate, with 7 patients (37%) experiencing grade 3 or 4 toxicity. In all, 16 patients who were evaluable for efficacy showed no objective response. We conclude that brequinar given at this dose and on this schedule has no significant activity in advanced squamous-cell carcinoma of the head and neck.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46923/1/280_2004_Article_BF00685106.pd

Biomarkers in advanced larynx cancer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102058/1/lary24245.pd

Weekly chemotherapy with radiation versus high‐dose cisplatin with radiation as organ preservation for patients with HPV‐positive and HPV‐negative locally advanced squamous cell carcinoma of the oropharynx

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106948/1/hed23339.pd

Individual Participant Data Network Meta-Analysis of Neoadjuvant Chemotherapy or Chemoradiotherapy in Esophageal or Gastroesophageal Junction Carcinoma

PURPOSE: The optimal neoadjuvant treatment for resectable carcinoma of the thoracic esophagus (TE) or gastroesophageal junction (GEJ) remains a matter of debate. We performed an individual participant data (IPD) network meta-analysis (NMA) of randomized controlled trials (RCTs) to study the effect of chemotherapy or chemoradiotherapy, with a focus on tumor location and histology subgroups. PATIENTS AND METHODS: All, published or unpublished, RCTs closed to accrual before December 31, 2015 and having compared at least two of the following strategies were eligible: upfront surgery (S), chemotherapy followed by surgery (CS), and chemoradiotherapy followed by surgery (CRS). All analyses were conducted on IPD obtained from investigators. The primary end point was overall survival (OS). The IPD-NMA was analyzed by a one-step mixed-effect Cox model adjusted for age, sex, tumor location, and histology. The NMA was registered in PROSPERO (CRD42018107158). RESULTS: IPD were obtained for 26 of 35 RCTs (4,985 of 5,807 patients) corresponding to 12 comparisons for CS-S, 12 for CRS-S, and four for CRS-CS. CS and CRS led to increased OS when compared with S with hazard ratio (HR) = 0.86 (0.75 to 0.99), P = .03 and HR = 0.77 (0.68 to 0.87), P &lt; .001 respectively. The NMA comparison of CRS versus CS for OS gave a HR of 0.90 (0.74 to 1.09), P = .27 (consistency P = .26, heterogeneity P = .0038). For CS versus S, a larger effect on OS was observed for GEJ versus TE tumors (P = .036). For the CRS versus S and CRS versus CS, a larger effect on OS was observed for women (P = .003, .012, respectively). CONCLUSION:Neoadjuvant chemotherapy and chemoradiotherapy were consistently better than S alone across histology, but with some variation in the magnitude of treatment effect by sex for CRS and tumor location for CS. A strong OS difference between CS and CRS was not identified.</p