Utility of the 70-Gene MammaPrint Assay for Prediction of Benefit From Extended Letrozole Therapy in the NRG Oncology/NSABP B-42 Trial.

Purpose: MammaPrint (MP) determines distant metastatic risk and may improve patient selection for extended endocrine therapy (EET). This study examined MP in predicting extended letrozole therapy (ELT) benefit in patients with early-stage breast cancer (BC) from the NSABP B-42 trial.

Patients And Methods: MP was tested in 1,866 patients randomly assigned to receive ELT or placebo.

Ten-year update: NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-42 randomized trial: extended letrozole therapy in early-stage breast cancer.

Background: The National Surgical Adjuvant Breast and Bowel Project B-42 trial evaluated extended letrozole therapy (ELT) in postmenopausal breast cancer patients who were disease free after 5 years of aromatase inhibitor (AI)-based therapy. Seven-year results demonstrated a nonstatistically significant trend in disease-free survival (DFS) in favor of ELT. We present 10-year outcome results.

Use of letrozole after aromatase inhibitor-based therapy in postmenopausal breast cancer (NRG Oncology/NSABP B-42): a randomised, double-blind, placebo-controlled, phase 3 trial.

Background: The optimal duration of extended therapy with aromatase inhibitors in patients with postmenopausal breast cancer is unknown. In the NSABP B-42 study, we aimed to determine whether extended letrozole treatment improves disease-free survival after 5 years of aromatase inhibitor-based therapy in women with postmenopausal breast cancer.

Methods: This randomised, double-blind, placebo-controlled, phase 3 trial was done in 158 centres in the USA, Canada, and Ireland.

Randomized Phase II Trial of Fulvestrant Plus Everolimus or Placebo in Postmenopausal Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer Resistant to Aromatase Inhibitor Therapy: Results of PrE0102.

Purpose The mammalian target of rapamycin inhibitor everolimus targets aberrant signaling through the PI3K/AKT/mammalian target of rapamycin pathway, a mechanism of resistance to anti-estrogen therapy in estrogen receptor (ER)-positive breast cancer. We hypothesized that everolimus plus the selective ER downregulator fulvestrant would be more efficacious than fulvestrant alone in ER-positive metastatic breast cancer resistant to aromatase inhibitor (AI) therapy. Patients and Methods This randomized, double-blind, placebo-controlled, phase II study included 131 postmenopausal women with ER-positive, human epidermal growth factor receptor 2-negative, AI-resistant metastatic breast cancer randomly assigned to fulvestrant (500 mg days 1 and 15 of cycle 1, then day 1 of cycles 2 and beyond) plus everolimus or placebo.

Patient-reported outcomes with anastrozole versus tamoxifen for postmenopausal patients with ductal carcinoma in situ treated with lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind, phase 3 clinical trial.

Background: The NSABP B-35 trial compared 5 years of treatment with anastrozole versus tamoxifen for reducing subsequent occurrence of breast cancer in postmenopausal patients with ductal carcinoma in situ. This report assesses the effect of these drugs on quality of life and symptoms.

Methods: The study was done at 333 hospitals in North America.

Anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind, phase 3 clinical trial.

Background: Ductal carcinoma in situ is currently managed with excision, radiotherapy, and adjuvant hormone therapy, usually tamoxifen. We postulated that an aromatase inhibitor would be safer and more effective. We therefore undertook this trial to compare anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy.

Neoadjuvant 5-FU or Capecitabine Plus Radiation With or Without Oxaliplatin in Rectal Cancer Patients: A Phase III Randomized Clinical Trial.

Background: National Surgical Adjuvant Breast and Bowel Project R-04 was designed to determine whether the oral fluoropyrimidine capecitabine could be substituted for continuous infusion 5-FU in the curative setting of stage II/III rectal cancer during neoadjuvant radiation therapy and whether the addition of oxaliplatin could further enhance the activity of fluoropyrimidine-sensitized radiation.

Methods: Patients with clinical stage II or III rectal cancer undergoing preoperative radiation were randomly assigned to one of four chemotherapy regimens in a 2x2 design: CVI 5-FU or oral capecitabine with or without oxaliplatin. The primary endpoint was local-regional tumor control.

Can pregabalin prevent paclitaxel-associated neuropathy?--An ACCRU pilot trial.

Purpose: Paclitaxel can cause an acute pain syndrome (P-APS), considered to be an acute form of neuropathy and chronic chemotherapy-induced peripheral neuropathy (CIPN). Anecdotal reports suggested that gabapentin may be helpful in the prevention of these toxicities. The purpose of this pilot study was to obtain data to support or refute the utility of pregabalin for the prevention of P-APS and CIPN.

NCCTG N0821 (Alliance): a phase II first-line study of pemetrexed, carboplatin, and bevacizumab in elderly patients with advanced nonsquamous non-small-cell lung cancer with good performance status.

Background: We hypothesized that the combination of bevacizumab, carboplatin, and pemetrexed will be an effective first-line regimen in fit, elderly patients with nonsquamous non-small-cell lung cancer.

Methods: Treatment-naïve, stage IIIB/IV nonsquamous non-small-cell lung cancer patients more than 70 years old with good performance status (Eastern Cooperative Oncology Group performance status 0-1) and adequate organ function were eligible. Carboplatin area under the curve 6, pemetrexed 500 mg/m, and bevacizumab 15 mg/kg were administered on day 1 of each 21-day cycle (up to six cycles) followed by maintenance pemetrexed and bevacizumab.

Comparative economics of a 12-gene assay for predicting risk of recurrence in stage II colon cancer.

Background: Prior economic analysis that compared the 12-gene assay to published patterns of care predicted the assay would improve outcomes while lowering medical costs for stage II, T3, mismatch-repair-proficient (MMR-P) colon cancer patients. This study assessed the validity of those findings with real-world adjuvant chemotherapy (aCT) recommendations from the US third-party payer perspective.

Methods: Costs and quality-adjusted life-years (QALYs) were estimated for stage II, T3, MMR-P colon cancer patients using guideline-compliant, state-transition probability estimation methods in a Markov model.

Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04.

Purpose: The optimal chemotherapy regimen administered concurrently with preoperative radiation therapy (RT) for patients with rectal cancer is unknown. National Surgical Adjuvant Breast and Bowel Project trial R-04 compared four chemotherapy regimens administered concomitantly with RT.

Patients And Methods: Patients with clinical stage II or III rectal cancer who were undergoing preoperative RT (45 Gy in 25 fractions over 5 weeks plus a boost of 5.

Prospective multicenter study of the impact of oncotype DX colon cancer assay results on treatment recommendations in stage II colon cancer patients.

The Oncotype DX colon cancer assay is a clinically validated predictor of recurrence risk in stage II colon cancer patients. This prospective study evaluated the impact of recurrence score (RS) results on physician recommendations regarding adjuvant chemotherapy in T3, mismatch repair-proficient (MMR-P) stage II colon cancer patients. Patients and Methods.

Comparative effectiveness of sphincter-sparing surgery versus abdominoperineal resection in rectal cancer: patient-reported outcomes in National Surgical Adjuvant Breast and Bowel Project randomized trial R-04.

Objective: National Surgical Adjuvant Breast and Bowel Project (NSABP) R-04 was a randomized controlled trial of neoadjuvant chemoradiotherapy in patients with resectable stage II-III rectal cancer. We hypothesized that patients who underwent abdominoperineal resection (APR) would have a poorer quality of life than those who underwent sphincter-sparing surgery (SSS).

Methods: To obtain patient-reported outcomes (PROs) we administered two symptom scales at baseline and 1 year postoperatively: the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) and the European Organization for the Research and Treatment of Cancer module for patients with Colorectal Cancer Quality of Life Questionnaire (EORTC QLQ-CR38).

The application of monoclonal antibodies in cancer diagnosis.

Cancer becomes the second leading cause of death in the world. An effective strategy for early diagnosis of the disease is key to reduce the mortality and morbidity. Development of effective monoclonal antibody (mAb)-based assays or diagnostic imaging techniques for detection of antigens and small molecules that are released from cancerous cells will enhance modern diagnostic medicine of cancer significantly.

The use of Ginkgo biloba for the prevention of chemotherapy-related cognitive dysfunction in women receiving adjuvant treatment for breast cancer, N00C9.

Purpose: Patients undergoing treatment for cancer often report problems with their cognitive function, which is an essential component of health-related quality of life. Pursuant to this, a two-arm randomized, placebo-controlled, double-blind, phase III clinical trial was conducted to evaluate Ginkgo biloba (EGB 761) for the prevention of chemotherapy-related cognitive dysfunction in patients with breast cancer.

Methods: Previously chemotherapy naïve women about to receive adjuvant chemotherapy for breast cancer were randomized to receive 60 mg of EGB 761 or a matching placebo twice daily.

Further data supporting that paclitaxel-associated acute pain syndrome is associated with development of peripheral neuropathy: North Central Cancer Treatment Group trial N08C1.

Background: Paclitaxel causes an acute pain syndrome (P-APS), occurring within days after each dose and usually abating within days. Paclitaxel also causes a more classic peripheral neuropathy, which steadily increases in severity with increasing paclitaxel total doses. Little detail is available regarding the natural history of these 2 syndromes, or any relationship between them, although a recent publication does provide natural history data about weekly paclitaxel, supporting an association between the severity of P-APS and eventual peripheral neuropathy symptoms.

Epratuzumab with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated diffuse large B-cell lymphoma.

Approximately 60% of patients with diffuse large B-cell non-Hodgkin lymphoma (DLBCL) are curable with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemoimmunotherapy. Epratuzumab (E) is an unlabeled anti-CD22 monoclonal antibody with efficacy in relapsed DLBCL. This phase 2 trial tested the safety and efficacy of combining E with R-CHOP (ER-CHOP) in untreated DLBCL.

Natural history of paclitaxel-associated acute pain syndrome: prospective cohort study NCCTG N08C1.

Purpose: The characteristics and natural history of the paclitaxel-acute pain syndrome (P-APS) and paclitaxel's more chronic neuropathy have not been well delineated.

Methods: Patients receiving weekly paclitaxel (70 to 90 mg/m(2)) completed daily questionnaires and weekly European Organisation for Research and Treatment of Cancer (EORTC) Chemotherapy-Induced Peripheral Neuropathy (CIPN) -20 instruments during the entire course of therapy.

Results: P-APS symptoms peaked 3 days after chemotherapy.

Phase II study of preoperative pemetrexed, carboplatin, and radiation followed by surgery for locally advanced esophageal cancer and gastroesophageal junction tumors.

Introduction: Based on favorable preliminary clinical data and the need to identify effective, well-tolerated neoadjuvant regimens for patients with locally advanced esophageal cancer, this clinical trial was undertaken.

Methods: This phase II study tested 500 mg/m neoadjuvant pemetrexed intravenously and carboplatin with an area under the curve of 6 intravenously on days 1 and 22 in conjunction with concomitant radiation of 5040 centigray, which was given in 28 daily fractions of 180 centigray. The primary endpoint was the rate of pathologic complete response.

Phase II trial of oral topotecan and intravenous carboplatin with G-CSF support in previously untreated patients with extensive stage small cell lung cancer: A North Central Cancer Treatment Group Study.

Objectives: The objective of this study was to evaluate the response rate and toxicities of the combination of oral topotecan and carboplatin in patients with untreated extensive stage small cell lung cancer (ES-SCLC). Previous studies have suggested improved outcomes with a topoisomerase I inhibitor in combination with a platinum agent.

Methods: Twenty-six patients with previously untreated, ES-SCLC were evaluable in this phase II trial.

Pretreatment quality of life is an independent prognostic factor for overall survival in patients with advanced stage non-small cell lung cancer.

Hypothesis: We conducted this pooled analysis to assess the prognostic value of pretreatment Quality of Life (QOL) assessments on overall survival (OS) in advanced non-small cell lung cancer (NSCLC).

Methods: Four hundred twenty patients with advanced NSCLC (stages IIIB with pleural effusion and IV) from six North Central Cancer Treatment Group trials were included in this study. QOL assessments included the single-item Uniscale (355 patients), Lung Cancer Symptom Scale (217 patients), and Functional Assessment of Cancer Therapy-Lung (197 patients).

Pilot study of Panax quinquefolius (American ginseng) to improve cancer-related fatigue: a randomized, double-blind, dose-finding evaluation: NCCTG trial N03CA.

Purpose: This pilot trial sought to investigate whether any of three doses of American ginseng (Panax quinquefolius) might help cancer-related fatigue. A secondary aim was to evaluate toxicity.

Methods: Eligible adults with cancer were randomized in a double-blind manner, to receive American ginseng in doses of 750, 1,000, or 2,000 mg/day or placebo given in twice daily dosing over 8 weeks.

Is social support associated with improved clinical outcomes in geriatric lung cancer patients? Observations from North Central Cancer Treatment Group Studies N9921 and N0222.

Background: Social support is defined as a network of family/friends who provide practical and emotional help. A sizable literature describes a direct relationship between social support and improved cancer clinical outcomes. This study explored the extent of social support and its potential association with survival and adverse events in geriatric lung cancer patients.