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

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:

BR.31

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

HELSINN - ANAM-17-21

Administered By
Duke Cancer Institute
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/

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

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

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

EMD Serono, Inc. Education Event

Administered By
Medicine, Medical Oncology
Role
Principal Investigator
Start Date
End Date

Publications:

Therapeutic outcomes in non-small cell lung cancer with BRAF mutations: a single institution, retrospective cohort study.

Background: Data describing therapeutic outcomes in patients with non-small cell lung cancers (NSCLC) with BRAF mutations remains limited. Methods: We conducted a retrospective cohort study of 31 patients with metastatic NSCLC treated at Duke University Hospital who had been identified by next-generation sequencing methods to bear a BRAF mutation in their tumor in order to evaluate clinical response to immunotherapy and chemotherapy. Results: Sixty-five percent of patients identified in this cohort were current or former smokers. Fourteen (45.2%) of patients had a BRAF V600E mutation and 17 (54.8%) had a non-V600E mutation. Median progression-free survival (PFS) in the 23 patients who received first-line chemotherapy was 6.4 months [95% confidence interval (CI), 2.3 to 13.0]. Overall survival (OS) in patients who received first-line chemotherapy showed a median survival of 18 months (95% CI, 7.4 to 28.6). OS comparing patients who had never received immunotherapy at any point was 18.4 months (95% CI, 4.1 to NE) compared to 19.0 months (95% CI, 9.9 to 28.6) in those who had received immunotherapy. We did not find a statistically significant difference in OS in patients with BRAF V600E, BRAF amplification, or non-V600E mutations. There was also no difference in OS in patients treated with targeted BRAF inhibitors compared to those who were not treated with targeted BRAF inhibitors. Conclusions: We describe therapeutic outcomes for patients with metastatic NSCLC with BRAF mutations treated with either cytotoxic chemotherapy or immunotherapy. Although the sample size is small, the survival curves do not suggest improved clinical activity in this population when treated with immunotherapy.
Authors
Tan, I; Stinchcombe, TE; Ready, NE; Crawford, J; Datto, MB; Nagy, RJ; Lanman, RB; Gu, L; Clarke, JM
MLA Citation
Tan, Irena, et al. “Therapeutic outcomes in non-small cell lung cancer with BRAF mutations: a single institution, retrospective cohort study..” Transl Lung Cancer Res, vol. 8, no. 3, June 2019, pp. 258–67. Pubmed, doi:10.21037/tlcr.2019.04.03.
URI
https://scholars.duke.edu/individual/pub1397860
PMID
31367539
Source
pubmed
Published In
Translational Lung Cancer Research
Volume
8
Published Date
Start Page
258
End Page
267
DOI
10.21037/tlcr.2019.04.03

Chemotherapy Dose Intensity and Overall Survival Among Patients With Advanced Breast or Ovarian Cancer.

BACKGROUND: The effects of chemotherapy dose intensity on patient outcomes in advanced cancer are not well understood. We studied the association between chemotherapy relative dose intensity (RDI) and overall survival (OS) among patients with advanced breast or ovarian cancer. PATIENTS AND METHODS: This retrospective cohort study included adults with advanced breast or ovarian cancer who received first-line myelosuppressive chemotherapy (January 2007 to December 2010) in US Oncology Network community practices. Dose delays ≥ 7 days, dose reductions ≥ 15%, and RDI relative to standard regimens were described. OS was measured by the Kaplan-Meier method and Cox proportional hazards models. RESULTS: Among 874 patients with advanced breast cancer, 33.2% experienced dose delays ≥ 7 days, 48.7% experienced dose reductions ≥ 15%, and 38.9% had RDI < 85%. In the multivariable Cox proportional hazards model, Eastern Cooperative Oncology Group performance status 1/2 versus 0 (hazard ratio [HR] = 1.45; 95% confidence interval [CI], 1.15-1.82) and triple-negative status (HR = 3.14; 95% CI, 1.15-8.62) were significantly associated with mortality. Among 170 patients with advanced ovarian cancer, 43.5% experienced dose delays ≥ 7 days, 48.2% experienced dose reductions ≥ 15%, and 46.5% had RDI < 85%. In the multivariable Cox proportional hazards model, dose reductions ≥ 15% (HR = 1.94; 95% CI, 1.09-3.46) and other tumor histology (vs. nonserous adenocarcinoma; HR = 3.55; 95% CI, 1.38-9.09) were significantly associated with mortality. CONCLUSION: Dose delays, dose reductions, and reduced RDI were common. In advanced breast cancer, health status and triple-negative disease were significantly associated with mortality. In advanced ovarian cancer, dose reductions and tumor histology were significantly associated with mortality. These results can help identify potential risk factors and characterize the effect of chemotherapy dose modification strategies on mortality.
Authors
Denduluri, N; Lyman, GH; Wang, Y; Morrow, PK; Barron, R; Patt, D; Bhowmik, D; Li, X; Bhor, M; Fox, P; Dhanda, R; Saravanan, S; Jiao, X; Garcia, J; Crawford, J
MLA Citation
Denduluri, Neelima, et al. “Chemotherapy Dose Intensity and Overall Survival Among Patients With Advanced Breast or Ovarian Cancer..” Clin Breast Cancer, vol. 18, no. 5, Oct. 2018, pp. 380–86. Pubmed, doi:10.1016/j.clbc.2018.02.003.
URI
https://scholars.duke.edu/individual/pub1311119
PMID
29622384
Source
pubmed
Published In
Clin Breast Cancer
Volume
18
Published Date
Start Page
380
End Page
386
DOI
10.1016/j.clbc.2018.02.003

Phase I study of pazopanib plus TH-302 in advanced solid tumors.

PURPOSE: To define the maximum tolerated dose (MTD), recommended phase II dose (RPTD), and assess safety and tolerability for the combination of pazopanib plus TH-302, an investigational hypoxia-activated prodrug (HAP), in adult patients with advanced solid tumors. METHODS: This was an open-label, non-randomized, single-center, phase I trial consisting 2 stages. Stage 1 was a standard "3 + 3" dose escalation design to determine safety and the RPTD for TH-302 plus pazopanib combination. Stage 2 was an expanded cohort to better describe the tolerability and toxicity profile at the MTD. Pazopanib was orally dosed at 800 mg daily on days 1-28 for all cohorts. TH-302 was administered intravenously on days 1, 8 and 15 of a 28-day cycle at doses of 340 mg/m2 (cohort 1) or 480 mg/m2 (cohort 2). Dose limiting toxicity (DLT) was assessed in the first 28-day cycle. Efficacy was assessed every 2 cycles. RESULTS: Thirty patients were enrolled between December 2011 and September 2013. In the dose escalation stage, 7 patients were enrolled in the 340 mg/m2 TH-302 cohort and 6 patients in the 480 mg/m2 TH-302 cohort. Ten patients were evaluable for DLT. DLTs included grade 2 intolerable esophagitis (n = 1) in the 340 mg/m2 TH-302 cohort, and grade 3 vaginal inflammation (n = 1) and grade 3 neutropenia with grade 3 thrombocytopenia (n = 1, same patient) in the 480 mg/m2 TH-302 cohort. The 340 mg/m2 TH-302 cohort was determined to be MTD and RPTD. The most common treatment-related adverse events were hematologic (anemia, neutropenia, and thrombocytopenia), nausea/vomiting, palmar-plantar erythrodysesthesia syndrome, constipation, fatigue, mucositis, anorexia, pain, and hypertension. Partial response (PR) was observed in 10% (n = 3) of patients, stable disease (SD) in 57% (n = 17), and progressive disease (PD) in 23% (n = 7). Due to toxicity, 3 patients were discontinued from study drug prior to first radiographic assessment but were included in these calculations. Disease control ≥6 months was observed in 37% of patients (n = 11). CONCLUSIONS: The RPTD for this novel combination is pazopanib 800 mg daily on days 1-28 plus TH-302 340 mg/m2 on days 1, 8 and 15 of each 28-day cycle. Preliminary activity was seen in treatment-refractory cancers and supports potential value of co-targeting tumor angiogenesis and tumor hypoxia.
Authors
Riedel, RF; Meadows, KL; Lee, PH; Morse, MA; Uronis, HE; Blobe, GC; George, DJ; Crawford, J; Niedzwiecki, D; Rushing, CN; Arrowood, CC; Hurwitz, HI
MLA Citation
Riedel, Richard F., et al. “Phase I study of pazopanib plus TH-302 in advanced solid tumors..” Cancer Chemother Pharmacol, vol. 79, no. 3, Mar. 2017, pp. 611–19. Pubmed, doi:10.1007/s00280-017-3256-2.
URI
https://scholars.duke.edu/individual/pub1226158
PMID
28238078
Source
pubmed
Published In
Cancer Chemother Pharmacol
Volume
79
Published Date
Start Page
611
End Page
619
DOI
10.1007/s00280-017-3256-2

Changing patterns of chemotherapy relative dose intensity and supportive care for aggressive B-cell non-Hodgkin lymphoma.

Maintaining high relative dose intensity (RDI) is associated with improved outcomes, especially in patients with aggressive B-cell non-Hodgkin lymphoma (NHL). To evaluate changes in practice, we examined RDI, chemotherapy treatment patterns, dose delays and reductions, neutropenia and related consequences, and supportive care in 500 patients with aggressive B-cell NHL treated between 2006-2009. We then compared the results to a previous study of patients treated between 1993-2001. Relative to the previous study, rituximab was a common addition to CHOP-21 (91% vs. 3%), more patients received an RDI ≥ 85% (68% vs. 52%), and fewer patients experienced dose reductions (21% vs. 35%), though incidences of dose delays were similar (26% vs. 23%). Incidences of febrile neutropenia (FN; 12% vs. 21%) and FN-related hospitalizations (10% vs. 16%) were lower. Finally, more patients received primary prophylaxis with colony-stimulating factors (75% vs. 12%). Together, these results illustrate evolving practice patterns for patients with aggressive B-cell NHL.
Authors
Lyman, GH; Crawford, J; Tomita, D; Whittaker, S; Dale, DC
MLA Citation
Lyman, Gary H., et al. “Changing patterns of chemotherapy relative dose intensity and supportive care for aggressive B-cell non-Hodgkin lymphoma..” Leuk Lymphoma, vol. 57, no. 2, 2016, pp. 283–90. Pubmed, doi:10.3109/10428194.2015.1045894.
URI
https://scholars.duke.edu/individual/pub872816
PMID
25926064
Source
pubmed
Published In
Leuk Lymphoma
Volume
57
Published Date
Start Page
283
End Page
290
DOI
10.3109/10428194.2015.1045894

Blood utilization and hemoglobin levels in cancer patients after label and coverage changes for erythropoiesis-stimulating agents.

A comprehensive literature search was performed to examine the influence of changes in erythropoietin-stimulating agent (ESA) label and reimbursement policies on utilization of red blood cell transfusions and patient hemoglobin levels in US cancer patients receiving chemotherapy or anemia management. Studies conducted in ESA-treated patients showed an increase in transfusion rates when comparing the post-intervention period with pre-intervention period (range of relative change: 15-125%). Results from studies conducted in patients receiving chemotherapy irrespective of anemia treatment were variable; single-institution-based studies tended to show a decrease in transfusion rates (range of relative change: -3.2 to -24.1%), while multiple-institution-based studies suggested an increase in transfusion rates (range of relative change: 12-182%). Studies showed decreases in hemoglobin levels during chemotherapy or at ESA initiation, and decreased ESA utilization.
Authors
Xu, H; Kaye, JA; Saltus, CW; Crawford, J; Gasal, E; Goodnough, LT
MLA Citation
Xu, Hairong, et al. “Blood utilization and hemoglobin levels in cancer patients after label and coverage changes for erythropoiesis-stimulating agents..” Expert Rev Hematol, vol. 7, no. 5, Oct. 2014, pp. 617–33. Pubmed, doi:10.1586/17474086.2014.943730.
URI
https://scholars.duke.edu/individual/pub1045858
PMID
25081548
Source
pubmed
Published In
Expert Review of Hematology
Volume
7
Published Date
Start Page
617
End Page
633
DOI
10.1586/17474086.2014.943730