Patients with human papillomavirus oropharyngeal cancer are highly curable but risk significant long-term toxic effects with standard therapy. This study investigated a de-escalation strategy of ...decreased adjuvant radiation therapy and chemotherapy after transoral robotic surgery, and reports on long-term functional and quality of life (QOL) outcomes.
Eligible patients had a p16-positive oropharyngeal cancer and ≤10 pack-year smoking history and underwent surgery followed by treatment with either 30 Gy delivered in 1.5-Gy fractions twice per day over 2 weeks with weekly docetaxel (15 mg/m2) if they had intermediate pathologic risk factors or 36 Gy in 1.8-Gy fractions twice per day over 2 weeks with the same chemotherapy if they had extranodal extension. Toxic effects, swallow function, and QOL were measured longitudinally.
Seventy-nine patients (89.9% male) were treated and eligible for toxic effect and functional evaluation. Dry mouth was the most common grade 1 toxic effect at 1 year (55.6%), 2 years (53.3%), and 3 years (49.2%). The cumulative rates of grade 2 toxic effects at 1, 2, and 3 years were 1.4%, 6.7%, and 6.8%, respectively. There were only 2 grade 3 toxic effects at ≥1 year, including a grade 3 fatigue at 2.5 years, and a grade 3 superficial soft tissue fibrosis at 4 years. There were no grade 4 to 5 toxic effects. No patients were percutaneous endoscopic gastrostomy–dependent. Swallow function improved by 12 months posttreatment. QOL improved over time by all measurement tools and most patients returned to baseline level of function and QOL.
De-escalated adjuvant therapy for select patients with human papillomavirus oropharyngeal cancer resulted in low rates of long-term toxic effects, excellent swallow outcomes, and preservation of global and xerostomia-related QOL.
Anthracycline use in metastatic breast cancer (MBC) is hindered by cumulative exposure limits and risk of cardiotoxicity. Pixantrone, a novel aza-anthracenedione with structural similarities to ...mitoxantrone and anthracyclines, is theorized to exhibit less cardiotoxicity, mainly due to lack of iron binding. We conducted a randomized phase II study to evaluate the efficacy and safety of 2 dosing schedules of pixantrone in patients with refractory HER2-negative MBC.
Intravenous pixantrone was administered at 180 mg/m2 every 3 weeks (group A) versus 85 mg/m2 on days 1, 8, and 15 of a 28-day cycle (group B). Primary endpoint was objective response rate (ORR) and secondary endpoints included progression-free survival (PFS), median 6-month PFS, overall survival (OS), safety, quality of life, and serial assessment of circulating tumor cells. A 20% ORR was targeted as sufficient for further testing of pixantrone in this patient population.
Forty-five patients were evaluable, with 2 confirmed partial responses in group A and 1 in group B. The trial was terminated due to insufficient activity. Overall median PFS and OS were 2.8 (95% confidence interval CI: 2.0-4.1) and 16.8 (95% CI: 8.9-21.6) months, respectively. Notable overall grade 3-4 adverse events were the following: neutrophil count decrease (62%), fatigue (16%), and decrease in ejection fraction (EF) (4%).
Pixantrone has insufficient activity in the second- and third-line MBC setting. It appears, however, to have limited cardiotoxicity. (ClinicalTrials.gov ID: NCT01086605).
Purpose
Missing scores complicate analysis of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) because patients with and without missing scores ...may systematically differ. We focus on optimal analysis methods for incomplete PRO-CTCAE items, with application to two randomized, double-blind, placebo-controlled, phase III trials.
Methods
In Alliance A091105 and COMET-2, patients completed PRO-CTCAE items before randomization and several times post-randomization (
N
= 64 and 107, respectively). For each trial, we conducted between-arm comparisons on the PRO-CTCAE via complete-case two-sample
t
-tests, mixed modeling with contrast, and multiple imputation followed by two-sample
t
-tests. Because interest lies in whether CTCAE grades can inform missing PRO-CTCAE scores, we performed multiple imputation with and without CTCAE grades as auxiliary variables to assess the added benefit of including them in the imputation model relative to only including PRO-CTCAE scores across all cycles.
Results
PRO-CTCAE completion rates ranged from 100.0 to 71.4% and 100.0 to 77.1% across time in A091105 and COMET-2, respectively. In both trials, mixed modeling and multiple imputation provided the most similar estimates of the average treatment effects. Including CTCAE grades in the imputation model did not consistently narrow confidence intervals of the average treatment effects because correlations for the same PRO-CTCAE item between different cycles were generally stronger than correlations between each PRO-CTCAE item and its corresponding CTCAE grade at the same cycle.
Conclusion
For between-arm comparisons, mixed modeling and multiple imputation are informative techniques for handling missing PRO-CTCAE scores. CTCAE grades do not provide added benefit for informing missing PRO-CTCAE scores. ClinicalTrials.gov Identifiers: NCT02066181 (Alliance A091105); NCT01522443 (COMET-2).
Low-grade dysplasia (LGD) is a risk factor for progression in Barrett's esophagus (BE). Progression estimates however vary and predictors of progression are not well established. We aimed to assess ...predictors of progression in a multicenter BE-LGD cohort.
All subjects with LGD (diagnosed by a GI pathologist) in a prospective BE registry were identified. Progression was defined development of HGD/EAC more than 12 months after index date of LGD diagnosis. Clinical, endoscopic factors and impact of histologic review by an independent panel of two GI pathologists were assessed as predictors of progression. Cox proportional hazard models were used to assess their association with risk of progression.
244 BE-LGD subjects met inclusion criteria. Their mean age was 63.2 years. 205 (84%) were males. The median follow up was 4.8 years. Fifty six patients were diagnosed with HGD/EAC in less than 12 months, while 14 progressed to HGD/EAC after 12 months, with an overall annual risk of progression of 1.2%. 29% of LGD subjects were downgraded to non-dysplastic and the remaining re-confirmed as LGD or indefinite dysplasia. The risk of progression in the reconfirmed LGD group was eight fold higher (hazards ratio: 7.6, 95% CI: 1.5-139.4) in a propensity score stratified model.
In this large BE-LGD cohort, progression risk increased substantially when an additional panel of two expert GI pathologists re-confirmed a LGD diagnosis. These BE subjects may be candidates for endoscopic therapy. LGD was a marker of prevalent HGD/EAC in 18% of patients.
In this phase 2 trial, we sought to evaluate the efficacy and safety of rituximab, cyclophosphamide, bortezomib, and dexamethasone (R-CyBorD) in patients with low-grade NHL. The regimen included ...rituximab on day 1 with weekly cyclophosphamide, dexamethasone, and bortezomib 1.3 mg/m
2
IV in a 28-day cycle. Twenty one patients were enrolled on the study. Median age was 69 years (range 51-80) and 17 (81%) patients had two or more prior treatments. Histologies included FL (n = 8), MCL (n = 8), and LPL/WM (n = 5). Hematologic toxicity and peripheral sensory neuropathy were the most common adverse events. With a median follow-up of 38.1 months, ORR was 13/21 (62%), with 4 (19%) CR. The ORR was 7/8 (88%) in FL and was 4/5 (80%) in LPL/WM. Median PFS and OS were 11.6 months and 54.8 months, respectively. R-CyBorD is an effective regimen in relapsed FL and LPL/WM patients with an acceptable safety profile.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Relapsed and refractory lymphoproliferative neoplasms have a significant need for novel therapeutic options. A phase I/II trial using a combination therapy of everolimus and lenalidomide in 58 ...patients with relapsed or refractory Hodgkin and non-Hodgkin lymphomas demonstrated a modest overall response of 27% and tolerability in a heavily pretreated patient population.
Treatment outcomes have improved in lymphoid malignancies but relapse remains inevitable for most patients. Everolimus and lenalidomide have shown clinical activity as single agents in patients with relapsed and refractory Hodgkin and non-Hodgkin lymphomas.
The present phase I/II trial for patients with relapsed and refractory lymphoid malignancy opened at Mayo Clinic from January 2011 to May 2013. The trial used a standard cohort 3 + 3 design to determine the maximum tolerated dose for the combination. Stem cell transplantation had failed in 27 of the patients (49%), 63% had stage IV disease, and ≥ 3 previous therapies had failed in 78%.
Of the 58 patients, enrolled, 55 were evaluable for analysis. The maximum tolerated dose was 5 mg/d for everolimus plus 10 mg/d for 21 days for lenalidomide. The most common grade ≥ 3 toxicities were hematologic and included neutropenia (56%), leukopenia (38%), and thrombocytopenia (33%). Seven patients discontinued the study because of adverse events. One patient died of disease progression. The overall response rate was 27% (15 of 55), with 38% (21 of 55) having stable disease.
The present phase I/II trial of everolimus and lenalidomide for R/R lymphoma has shown the combination to be tolerable, with neutropenia as the main dose-limiting toxicity. Encouraging responses were seen in this heavily pretreated group, and the patients with a response had meaningful duration of response.
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