Susan Griffing

Bio: Susan Griffing is an academic researcher from Genentech. The author has contributed to research in topics: Bevacizumab & Colorectal cancer. The author has an hindex of 5, co-authored 6 publications receiving 11480 citations. Previous affiliations of Susan Griffing include University of California, San Francisco.

Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer

Abstract: background Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promising preclinical and clinical activity against metastatic colorectal cancer, particularly in combination with chemotherapy. methods Of 813 patients with previously untreated metastatic colorectal cancer, we randomly assigned 402 to receive irinotecan, bolus fluorouracil, and leucovorin (IFL) plus bevacizumab (5 mg per kilogram of body weight every two weeks) and 411 to receive IFL plus placebo. The primary end point was overall survival. Secondary end points were progression-free survival, the response rate, the duration of the response, safety, and the quality of life. results The median duration of survival was 20.3 months in the group given IFL plus bevacizumab, as compared with 15.6 months in the group given IFL plus placebo, corresponding to a hazard ratio for death of 0.66 (P<0.001). The median duration of progressionfree survival was 10.6 months in the group given IFL plus bevacizumab, as compared with 6.2 months in the group given IFL plus placebo (hazard ratio for disease progression, 0.54; P<0.001); the corresponding rates of response were 44.8 percent and 34.8 percent (P=0.004). The median duration of the response was 10.4 months in the group given IFL plus bevacizumab, as compared with 7.1 months in the group given IFL plus placebo (hazard ratio for progression, 0.62; P=0.001). Grade 3 hypertension was more common during treatment with IFL plus bevacizumab than with IFL plus placebo (11.0 percent vs. 2.3 percent) but was easily managed. conclusions The addition of bevacizumab to fluorouracil-based combination chemotherapy results in statistically significant and clinically meaningful improvement in survival among patients with metastatic colorectal cancer.

Phase II, Randomized Trial Comparing Bevacizumab Plus Fluorouracil (FU)/Leucovorin (LV) With FU/LV Alone in Patients With Metastatic Colorectal Cancer

Abstract: Purpose: This phase II trial investigated the safety and efficacy of two doses of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, plus fluorouracil (FU)/leucovorin (LV) versus FU/LV alone in patients with metastatic colorectal cancer. Patients and Methods: One hundred four previously untreated patients with measurable metastatic colorectal cancer were randomly assigned to one of the following three treatment groups: 36 to FU (500 mg/m2)/LV (500 mg/m2) alone, 35 to FU/LV + low-dose bevacizumab (5 mg/kg every 2 weeks), and 33 to FU/LV + high-dose bevacizumab (10 mg/kg every 2 weeks). FU/LV was given weekly for the first 6 weeks of each 8-week cycle. Results: Compared with the FU/LV control arm, treatment with bevacizumab (at both dose levels) plus FU/LV resulted in higher response rates (control arm, 17%, 95% confidence interval [CI], 7% to 34%; low-dose arm, 40%, 95% CI, 24% to 58%; high-dose arm, 24%, 95% CI, 12% to 43%), longer median time to disease progression (control arm, 5....

Post-progression therapy (PPT) effect on survival in AVF2107, a phase III trial of bevacizumab in first-line treatment of metastatic colorectal cancer (mCRC)

Abstract: 3517 Background: Bevacizumab [Avastin (BV)], a recombinant humanized monoclonal antibody against VEGF, significantly prolongs overall survival (OS) when added to 1st-line chemotherapy for mCRC. BV ...

Bevacizumab (a monoclonal antibody to vascular endothelial growth factor) to prolong progression-free survival in first-line colorectal cancer (CRC) in subjects who are not suitable candidates for first-line CPT-11

Abstract: 3516 Background: Bevacizumab [Avastin (BV)] is a recombinant, humanized monoclonal antibody directed against vascular endothelial growth factor. As presented at ASCO 2003, the addition of BV to IFL...

Phase I I, R andomized T rial C omparing B evacizumab P lus Fluorouracil ( FU)/Leucovorin ( LV) W ith F U/LV A lone i n Patients W ith M etastatic C olorectal C ancer

Abstract: Purpose: This phase II trial investigated the safety and efficacy of two doses of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, plus fluorouracil (FU)/leucovorin (LV) versus FU/LV alone in patients with metastatic colorectal cancer. Patients and Methods: One hundred four previously untreated patients with measurable metastatic colorectal cancer were randomly assigned to one of the following three treatment groups: 36 to FU (500 mg/m 2 )/LV (500 mg/m 2 ) alone, 35 to FU/LV low-dose bevacizumab (5 mg/kg every 2 weeks), and 33 to FU/LV high-dose bevacizumab (10 mg/kg every 2 weeks). FU/LV was given weekly for the first 6 weeks of each 8-week cycle. Results: Compared with the FU/LV control arm, treatment with bevacizumab (at both dose levels) plus FU/LV resulted in higher response rates (control arm, 17%, 95% confidence interval [CI], 7% to 34%; low-dose arm, 40%, 95% CI, 24% to 58%; high-dose arm, 24%, 95% CI, 12% to 43%), longer median time to disease progression (control arm, 5.2 months, 95% CI, 3.5 to 5.6 months; low-dose arm, 9.0 months, 95% CI, 5.8 to 10.9 months; high-dose arm, 7.2 months, 95% CI, 3.8 to 9.2 months), and longer median survival (control arm, 13.8 months; 95% CI, 9.1 to 23.0 months; low-dose arm, 21.5 months, 95% CI, 17.3 to undetermined; high-dose arm, 16.1 months; 95% CI, 11.0 to 20.7 months). After cross-over, two of 22 patients had a partial response to bevacizumab alone. Thrombosis was the most significant adverse event and was fatal in one patient. Hypertension, proteinuria, and epistaxis were other potential safety concerns. Conclusion: The encouraging results of this randomized trial support further study of bevacizumab 5 mg/kg plus chemotherapy as first-line therapy for metastatic colorectal cancer. J Clin Oncol 21:60-65. © 2003 by American Society of Clinical Oncology.

Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer

Abstract: background Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promising preclinical and clinical activity against metastatic colorectal cancer, particularly in combination with chemotherapy. methods Of 813 patients with previously untreated metastatic colorectal cancer, we randomly assigned 402 to receive irinotecan, bolus fluorouracil, and leucovorin (IFL) plus bevacizumab (5 mg per kilogram of body weight every two weeks) and 411 to receive IFL plus placebo. The primary end point was overall survival. Secondary end points were progression-free survival, the response rate, the duration of the response, safety, and the quality of life. results The median duration of survival was 20.3 months in the group given IFL plus bevacizumab, as compared with 15.6 months in the group given IFL plus placebo, corresponding to a hazard ratio for death of 0.66 (P<0.001). The median duration of progressionfree survival was 10.6 months in the group given IFL plus bevacizumab, as compared with 6.2 months in the group given IFL plus placebo (hazard ratio for disease progression, 0.54; P<0.001); the corresponding rates of response were 44.8 percent and 34.8 percent (P=0.004). The median duration of the response was 10.4 months in the group given IFL plus bevacizumab, as compared with 7.1 months in the group given IFL plus placebo (hazard ratio for progression, 0.62; P=0.001). Grade 3 hypertension was more common during treatment with IFL plus bevacizumab than with IFL plus placebo (11.0 percent vs. 2.3 percent) but was easily managed. conclusions The addition of bevacizumab to fluorouracil-based combination chemotherapy results in statistically significant and clinically meaningful improvement in survival among patients with metastatic colorectal cancer.

The biology of VEGF and its receptors.

Abstract: Vascular endothelial growth factor (VEGF) is a key regulator of physiological angiogenesis during embryogenesis, skeletal growth and reproductive functions. VEGF has also been implicated in pathological angiogenesis associated with tumors, intraocular neovascular disorders and other conditions. The biological effects of VEGF are mediated by two receptor tyrosine kinases (RTKs), VEGFR-1 and VEGFR-2, which differ considerably in signaling properties. Non-signaling co-receptors also modulate VEGF RTK signaling. Currently, several VEGF inhibitors are undergoing clinical testing in several malignancies. VEGF inhibition is also being tested as a strategy for the prevention of angiogenesis, vascular leakage and visual loss in age-related macular degeneration.

Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer

Abstract: bevacizumab, as compared with 10.3 months in the chemotherapy-alone group (hazard ratio for death, 0.79; P = 0.003). The median progression-free survival in the two groups was 6.2 and 4.5 months, respectively (hazard ratio for disease progression, 0.66; P<0.001), with corresponding response rates of 35% and 15% (P<0.001). Rates of clinically significant bleeding were 4.4% and 0.7%, respectively (P<0.001). There were 15 treatment-related deaths in the chemotherapy-plus-bevacizumab group, including 5 from pulmonary hemorrhage. Conclusions The addition of bevacizumab to paclitaxel plus carboplatin in the treatment of selected patients with non–small-cell lung cancer has a significant survival benefit with the risk of increased treatment-related deaths. (ClinicalTrials.gov number, NCT00021060.)

Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy

Abstract: Solid tumors require blood vessels for growth, and many new cancer therapies are directed against the tumor vasculature. The widely held view is that these antiangiogenic therapies should destroy the tumor vasculature, thereby depriving the tumor of oxygen and nutrients. Here, I review emerging evidence supporting an alternative hypothesis-that certain antiangiogenic agents can also transiently "normalize" the abnormal structure and function of tumor vasculature to make it more efficient for oxygen and drug delivery. Drugs that induce vascular normalization can alleviate hypoxia and increase the efficacy of conventional therapies if both are carefully scheduled. A better understanding of the molecular and cellular underpinnings of vascular normalization may ultimately lead to more effective therapies not only for cancer but also for diseases with abnormal vasculature, as well as regenerative medicine, in which the goal is to create and maintain a functionally normal vasculature.

Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer.

Abstract: Background We investigated the efficacy of cetuximab plus irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for metastatic colorectal cancer and sought associations between the mutation status of the KRAS gene in tumors and clinical response to cetuximab. Methods We randomly assigned patients with epidermal growth factor receptor–positive colorectal cancer with unresectable metastases to receive FOLFIRI either alone or in combination with cetuximab. The primary end point was progression-free survival. Results A total of 599 patients received cetuximab plus FOLFIRI, and 599 received FOLFIRI alone. The hazard ratio for progression-free survival in the cetuximab–FOLFIRI group as compared with the FOLFIRI group was 0.85 (95% confidence interval [CI], 0.72 to 0.99; P=0.048). There was no significant difference in the overall survival between the two treatment groups (hazard ratio, 0.93; 95% CI, 0.81 to 1.07; P=0.31). There was a significant interaction between treatment group and KRAS ...