Jeffrey Crawford

Overview:

1. Lung cancer/new treatment approaches.
2. Clinical trials of hematopoietic growth factors, biological agents and targeted drug development.
3. Cancer in the elderly and supportive care

Accomplishments

1. Lead Investigator of the U. S. multicenter, randomized trial of Filgrastim (G-CSF, Neupogen) to reduce the morbidity of chemotherapy-related neutropenia, leading to FDA approval 2/91.
2. Lead Investigator of the U. S. multicenter, randomized trial of Vinorelbine (Navelbine) in treatment of patients with advanced non small cell carcinoma of lung (NSCLC), leading to FDA approval 12/94.
3. Principal Investigator in initial phase I clinical trials of stem cell factor (SCF), megakaryocyte growth and development factor (MGDF), pegylated granulocyte-colony-stimulating factor and other novel hematopoietic growth factors.

Positions:

George Barth Geller Distinguished Professor for Research in Cancer

Medicine, Medical Oncology
School of Medicine

Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1974

Ohio State University

Grants:

A PHASE III PROSPECTIVE DOUBLE BLIND PLACEBO CONTROLLED RANDOMIZED STUDY OF ADJUVANT MEDI4736 IN COMPLETELY RESECTED NON-SMALL CELL LUNG CANCER

Administered By
Duke Cancer Institute
Awarded By
Clinipace, Inc.
Role
Principal Investigator
Start Date
End Date

PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ANAMORELIN HCL

Administered By
Duke Cancer Institute
Awarded By
Helsinn Healthcare S.A.
Role
Principal Investigator
Start Date
End Date

A phase II, Open-label, single-arm study to assess the safety and efficacy of AZD9291 in patients with locally advanced/mteastatic non-small cell lung cancer whose disease has progressed with previous epidermal growth factor receptor

Administered By
Duke Cancer Institute
Awarded By
AstraZeneca AB
Role
Principal Investigator
Start Date
End Date

Phase II anetumab ravtansine as 2nd line treatment for malignant pleural mesothelioma

Administered By
Duke Cancer Institute
Awarded By
Bayer HealthCare AG
Role
Principal Investigator
Start Date
End Date

EMD Serono, Inc. Education Event

Administered By
Medicine, Medical Oncology
Awarded By
EMD Serono Inc
Role
Principal Investigator
Start Date
End Date

Publications:

Use of prophylactic pegfilgrastim for chemotherapy-induced neutropenia in the US: A review of adherence to present guidelines for usage.

Evidence-based US guidelines provide recommendations for the use of granulocyte colony-stimulating factor (G-CSF) as supportive therapy in patients with cancer receiving chemotherapy. Pegfilgrastim is recommended for FN prophylaxis in patients with non-myeloid malignancies receiving a high-risk chemotherapy regimen, or an intermediate-risk regimen if one or more risk factors are present. The guidelines highlight the patient characteristics and chemotherapy regimens for solid tumors and hematologic malignancies that may influence a patient's overall risk of FN and may benefit from pegfilgrastim support. This review aimed to evaluate how pegfilgrastim use in patients with cancer receiving myelosuppressive chemotherapy in routine clinical practice aligns with evidence-based US guidelines. Examination of the literature revealed widespread deviation in relation to under- and over-prescribing, and timing of administration in US clinical practice. Pegfilgrastim is often over-prescribed in patients receiving palliative chemotherapy and those at low risk of FN. Potential under-prescribing of pegfilgrastim was also observed. In this literature search, data that appear to support same-day administration of pegfilgrastim were from uncontrolled studies that were limited in size. Analyses of healthcare claims data clearly favored next-day use, with statistically significant increases in FN incidence among patients receiving same-day pegfilgrastim versus those treated 1-4 days post-chemotherapy. Earlier-than-recommended administration typically occurs at the physician's discretion where next-day administration might present barriers to the patient receiving supportive therapy.There is a need to ensure appropriate prescribing to optimize patient outcomes, as deviation from the guideline recommendations was associated with increased incidence of FN and hospitalization.
Authors
Crawford, J; Moore, DC; Morrison, VA; Dale, D
MLA Citation
Crawford, Jeffrey, et al. “Use of prophylactic pegfilgrastim for chemotherapy-induced neutropenia in the US: A review of adherence to present guidelines for usage.Cancer Treat Res Commun, vol. 29, Sept. 2021, p. 100466. Pubmed, doi:10.1016/j.ctarc.2021.100466.
URI
https://scholars.duke.edu/individual/pub1499597
PMID
34655862
Source
pubmed
Published In
Cancer Treatment and Research Communications
Volume
29
Published Date
Start Page
100466
DOI
10.1016/j.ctarc.2021.100466

Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760).

<h4>Introduction</h4>S1400F is a non-match substudy of Lung Cancer Master Protocol (Lung-MAP) evaluating the immunotherapy combination of durvalumab and tremelimumab to overcome resistance to anti-programmed death ligand 1 (PD-(L)1) therapy in patients with advanced squamous lung carcinoma (sq non-small-cell lung cancer (NSCLC)).<h4>Methods</h4>Patients with previously treated sqNSCLC with disease progression after anti-PD-(L)1 monotherapy, who did not qualify for any active molecularly targeted Lung-MAP substudies, were eligible. Patients received tremelimumab 75 mg plus durvalumab 1500 mg once every 28 days for four cycles then durvalumab alone every 28 days until disease progression. The primary endpoint was the objective response rate (RECIST V.1.1). Primary and acquired resistance cohorts, defined as disease progression within 24 weeks versus ≥24 weeks of starting prior anti-PD-(L)1 therapy, were analyzed separately and an interim analysis for futility was planned after 20 patients in each cohort were evaluable for response.<h4>Results</h4>A total of 58 eligible patients received drug, 28 with primary resistance and 30 with acquired resistance to anti-PD-(L)1 monotherapy. Grade ≥3 adverse events at least possibly related to treatment were seen in 20 (34%) patients. The response rate in the primary resistance cohort was 7% (95% CI 0% to 17%), with one complete and one partial response. No responses were seen in the acquired resistance cohort. In the primary and resistance cohorts the median progression-free survival was 2.0 months (95% CI 1.6 to 3.0) and 2.1 months (95% CI 1.6 to 3.2), respectively, and overall survival was 7.7 months (95% CI 4.0 to 12.0) and 7.6 months (95% CI 5.3 to 10.2), respectively.<h4>Conclusion</h4>Durvalumab plus tremelimumab had minimal activity in patients with advanced sqNSCLC progressing on prior anti-PD-1 therapy.<b>Trial registration number</b>NCT03373760.
Authors
Leighl, NB; Redman, MW; Rizvi, N; Hirsch, FR; Mack, PC; Schwartz, LH; Wade, JL; Irvin, WJ; Reddy, SC; Crawford, J; Bradley, JD; Stinchcombe, TE; Ramalingam, SS; Miao, J; Minichiello, K; Herbst, RS; Papadimitrakopoulou, VA; Kelly, K; Gandara, DR
MLA Citation
Leighl, Natasha B., et al. “Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760).Journal for Immunotherapy of Cancer, vol. 9, no. 8, Aug. 2021. Epmc, doi:10.1136/jitc-2021-002973.
URI
https://scholars.duke.edu/individual/pub1494986
PMID
34429332
Source
epmc
Published In
Journal for Immunotherapy of Cancer
Volume
9
Published Date
DOI
10.1136/jitc-2021-002973

Prophylactic pegfilgrastim to prevent febrile neutropenia among patients receiving biweekly (Q2W) chemotherapy regimens: a systematic review of efficacy, effectiveness and safety.

<h4>Background</h4>Pegfilgrastim, a long-acting granulocyte colony-stimulating factor (G-CSF), is commonly used to prevent febrile neutropenia (FN), a potentially life-threatening complication, following myelosuppressive chemotherapy. The FDA label for pegfilgrastim specifies that it should not be administered 14 days before or within 24 h of administration of myelosuppressive chemotherapy, precluding the use of pegfilgrastim in biweekly (Q2W) regimens. The National Comprehensive Cancer Network and the European Organisation for Research and Treatment of Cancer guidelines support the use of prophylactic pegfilgrastim in patients receiving Q2W regimens. The objective of this study was to systematically review evidence from randomized clinical trials (RCTs) and observational studies that describe the effectiveness and safety of prophylactic pegfilgrastim in preventing FN among patients receiving Q2W regimens.<h4>Methods</h4>An Ovid MEDLINE, Embase, and Cochrane Library literature search was conducted to evaluate the evidence regarding efficacy, effectiveness, and safety of prophylactic pegfilgrastim versus no prophylactic pegfilgrastim or prophylaxis with other G-CSF in patients who were receiving Q2W chemotherapy regimens with high (> 20%) or intermediate (10-20%) risk of FN for a non-myeloid malignancy. Studies that addressed absolute or relative risk of FN, grade 1-4 neutropenia, all-cause or any hospitalization, dose delays or dose reductions, adverse events, or mortality were included. Studies where the comparator was a Q3W chemotherapy regimen with primary prophylactic pegfilgrastim were also included.<h4>Results</h4>The initial literature search identified 2258 publications. Thirteen publications met the eligibility criteria, including eight retrospective, one prospective, one phase 1 dose escalation study, and three RCTs. In nine of the 13 studies reporting incidence of FN, and in seven of the nine studies reporting incidence of neutropenia, administration of prophylactic pegfilgrastim in patients receiving Q2W regimens resulted in decreased or comparable rates of FN or neutropenia compared with patients receiving filgrastim, no G-CSF, lipefilgrastim or pegfilgrastim in Q3W regimens. In six of the nine studies reporting safety data, lower or comparable safety profiles were observed between pegfilgrastim and comparators.<h4>Conclusions</h4>In a variety of non-myeloid malignancies, administration of prophylactic pegfilgrastim was efficacious in reducing the risk of FN in patients receiving high- or intermediate-risk Q2W regimens, with an acceptable safety profile.<h4>Trial registration</h4>PROSPERO registration no: CRD42019155572 .
Authors
Mahtani, R; Crawford, J; Flannery, SM; Lawrence, T; Schenfeld, J; Gawade, PL
MLA Citation
URI
https://scholars.duke.edu/individual/pub1484271
PMID
34044798
Source
epmc
Published In
Bmc Cancer
Volume
21
Published Date
Start Page
621
DOI
10.1186/s12885-021-08258-w

Treatment at Integrated Centers Might Bridge the Academic-Community Survival Gap in Patients With Metastatic Non-Small Cell Carcinoma of the Lung.

BACKGROUND: Non-small cell lung cancer (NSCLC) is responsible for the most cancer-related deaths in the United States. A better understanding of treatment-related disparities and ways to address them are important to improving survival for patients with metastatic NSCLC. MATERIALS AND METHODS: We performed a retrospective analysis using the National Cancer Database. Included in this analysis were 107,116 patients with metastatic NSCLC who were treated at academic centers (AC), community-based centers (CC), and integrated centers (IC) between 2004 and 2015. The primary end point was overall survival, with comparisons of AC, CC, and IC. RESULTS: The survival disparity between AC and CC continued to grow over the study period, from a 5.7% difference in 2-year survival to a 7.5% difference. Treatment at IC was initially associated with survival similar to CC (hazard ratio [HR], 0.93), however, later in the study period treatment at IC improved (HR, 0.74) outpacing the improvement in survival in CC (HR, 0.82) but not to the same degree as the improvement in AC (HR, 0.64). The improvement in survival at IC was noted predominantly in patients with adenocarcinoma (HR, 0.72; P < .001) but not in squamous-cell carcinoma (HR, 0.89; P value not significant). CONCLUSION: Treatment of metastatic NSCLC at IC was associated with improved survival during our study period compared with treatment at CC. This appeared to be histology-dependent, suggesting a treatment-related improvement in survival because over this period newer therapies were preferentially available for adenocarcinoma. Integrating care across treatment facilities might be one way to bridge the growing gap in survival between AC and CC.
Authors
Ramalingam, S; Dinan, MA; Crawford, J
MLA Citation
Ramalingam, Sendhilnathan, et al. “Treatment at Integrated Centers Might Bridge the Academic-Community Survival Gap in Patients With Metastatic Non-Small Cell Carcinoma of the Lung.Clin Lung Cancer, vol. 22, no. 4, July 2021, pp. e646–53. Pubmed, doi:10.1016/j.cllc.2020.12.013.
URI
https://scholars.duke.edu/individual/pub1474599
PMID
33582071
Source
pubmed
Published In
Clin Lung Cancer
Volume
22
Published Date
Start Page
e646
End Page
e653
DOI
10.1016/j.cllc.2020.12.013

Role of dietary carbohydrates on risk of lung cancer.

OBJECTIVES: Inconsistent findings have been reported on the link between dietary carbohydrates and lung cancer. This study aims to comprehensively evaluate the role of dietary carbohydrates on lung cancer risk. MATERIALS AND METHODS: The prospective study is based on the PLCO trial, which recruited 113,096 eligible participants across the United States. Participants had to have completed baseline and diet history questionnaires. The incidence of lung cancer was acquired through self-report and medical record follow-up. A multivariable logistic model adjusted for confounders was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) of dietary carbohydrates, fiber, whole grains, glycemic index (GI) and glycemic load (GL) for lung cancer. Similar methods were applied in analyzing the carbohydrates and fiber from different food sources. Multinomial logistic models were used for sensitivity analysis with lung cancer subtypes as outcomes. RESULTS: Dietary carbohydrates and GL were inversely associated with lung cancer incidence in the PLCO population. Among various carbohydrates, 30-g daily consumption of dietary fiber was related to a lower risk of lung cancer (fourth vs first quartile OR: 0.62, 95 % CI: 0.54-0.72) compared with 8.8-g. Furthermore, consuming whole grains 2.3 servings per day as opposed to 0.3 servings per day was associated with a lower risk of lung cancer (OR: 0.73, 95 % CI: 0.64-0.83). A higher risk of lung cancer was seen for the consumption of high-GI food (OR: 1.19, 95 % CI: 1.05-1.35) and refined carbohydrates from soft drinks (OR: 1.23, 95 % CI: 1.04-1.46). CONCLUSION: Carbohydrates and fiber from fruits, vegetables and whole grains are associated with lower lung cancer risk. Refined carbohydrates from processed food, such as soft drinks, appear to increase risk.
Authors
Tao, J; Jatoi, A; Crawford, J; Lam, WWT; Ho, JC; Wang, X; Pang, H
MLA Citation
Tao, Jun, et al. “Role of dietary carbohydrates on risk of lung cancer.Lung Cancer, vol. 155, May 2021, pp. 87–93. Pubmed, doi:10.1016/j.lungcan.2021.03.009.
URI
https://scholars.duke.edu/individual/pub1476522
PMID
33756357
Source
pubmed
Published In
Lung Cancer
Volume
155
Published Date
Start Page
87
End Page
93
DOI
10.1016/j.lungcan.2021.03.009