About Avastin: Dosing

Avastin dosing in approved cancer types

Avastin is administered as a solution for intravenous (IV) infusion at the following doses and schedules^[1]:

Tumor type	Combination regimen	Avastin dose	Avastin schedule
MCRC	IFL* (First-line Study 2107)	5 mg/kg IV	Every 2 weeks
	FOLFOX4^† (Second-line Study E3200)	10 mg/kg IV	Every 2 weeks
	Fluoropyrimidine-based chemotherapy in patients who had progressed on a first-line Avastin-containing regimen^‡ (First- through second-line TML study^§)	5 mg/kg IV	Every 2 weeks
		7.5 mg/kg IV	Every 3 weeks
NSCLC^\|\|	PC	15 mg/kg IV	Every 3 weeks
mRCC^¶	IFN	10 mg/kg IV	Every 2 weeks
CC^#	Cisplatin/paclitaxel or topotecan/paclitaxel	15 mg/kg IV	Every 3 weeks
OC	Carboplatin and paclitaxel**	15 mg/kg IV	Every 3 weeks
psOC^††	Carboplatin and gemcitabine	15 mg/kg IV	Every 3 weeks
psOC^††	Carboplatin and paclitaxel	15 mg/kg IV	Every 3 weeks
prOC^‡‡	Paclitaxel (weekly)	10 mg/kg IV	Every 2 weeks
	PLD
	Topotecan (weekly)
	Topotecan (every 3 weeks)	15 mg/kg IV	Every 3 weeks
rGBM^§§	None (single agent)	10 mg/kg IV	Every 2 weeks
HCC^IIII	Atezolizumab	15 mg/kg IV	Every 3 weeks

*5 mg/kg IV dose evaluated in first-line MCRC in combination with 5-fluorouracil (5-FU)/leucovorin (LV)/irinotecan (IFL).
^†10 mg/kg IV dose evaluated in second-line, Avastin-naive MCRC patients in combination with 5-FU/LV/oxaliplatin (FOLFOX4).^[1,4]
^‡5 mg/kg IV every 2 weeks and 7.5 mg/kg IV every 3 weeks doses evaluated, in combination with fluoropyrimidine and either irinotecan- or oxaliplatin-containing chemotherapy, in MCRC patients who had progressed on a first-line Avastin-containing regimen.
^§TML=Treatment through Multiple Lines (first and second line).
^||15 mg/kg IV dose evaluated in first-line locally advanced or metastatic non-squamous NSCLC in combination with paclitaxel + carboplatin (PC). Avastin plus PC was given for up to 6 cycles, after which Avastin was continued alone until disease progression or unacceptable toxicity.
^¶10 mg/kg IV dose evaluated in mRCC in combination with interferon alfa (IFN). AVOREN protocol allowed for IFN dose escalation (attaining a dose of 9 million international units [MIU] within the first 2 weeks), reduction, or discontinuation. IFN was discontinued after 52 weeks or earlier.^[3,14]
^#15 mg/kg IV dose evaluated in CC in combination with cisplatin/paclitaxel or topotecan/paclitaxel. Treatment was given until disease progression or unacceptable toxicity.
**15 mg/kg IV dose evaluated in stage III or IV OC following initial surgical resection in combination with carboplatin and paclitaxel. Avastin plus carboplatin and paclitaxel was given for up to 6 cycles, after which Avastin was continued alone for a total of up to 22 cycles, or until disease progression or unacceptable toxicity.
^††15 mg/kg IV dose evaluated in psOC in combination with carboplatin and paclitaxel for 6-8 cycles or carboplatin and gemcitabine for 6-10 cycles after which Avastin was continued alone until disease progression.
^‡‡10 mg/kg IV dose evaluated in prOC in combination with weekly paclitaxel, PLD (pegylated liposomal doxorubicin), or weekly topotecan, and 15 mg/kg IV dose evaluated in combination with topotecan administered every 3 weeks. Treatment was given until disease progression or unacceptable toxicity.
^§§10 mg/kg IV dose evaluated as a single agent for rGBM that has progressed following prior therapy.
^IIII15 mg/kg IV dose evaluated in HCC after IV administration of 1200 mg of atezolizumab on the same day, every 3 weeks until disease progression or unacceptable toxicity.

Recurrent glioblastoma (rGBM)
Avastin is indicated for the treatment of recurrent glioblastoma in adults.

Important treatment considerations—Women of childbearing potential

Avastin increases the risk of ovarian failure and may impair fertility. Inform females of reproductive potential of the risk of ovarian failure prior to the first dose of Avastin
Long-term effects of Avastin exposure on fertility are unknown
Patients should also use effective contraception during treatment and for 6 months following the last dose of Avastin
Nursing mothers should not breastfeed during treatment and for 6 months following their last dose of treatment

Duration of Avastin treatment

The FDA-approved Prescribing Information addresses the duration of Avastin treatment^[1]
Patients should continue treatment until disease progression or unacceptable toxicity.

Important treatment considerations—Dose modifications

No dose reductions for Avastin are recommended.

Dose Modifications for Adverse Reactions

Adverse reaction	Severity	Dosage modification
Gastrointestinal Perforation and Fistulae	Gastrointestinal perforation, any grade Tracheoesophageal fistula, any grade Fistula, Grade 4 Fistula formation involving any internal organ	Discontinue Avastin
Wound Healing Complications	Any	Withhold Avastin until adequate wound healing. The safety of resumption of Avastin after resolution of wound healing complications has not been established.
Wound Healing Complications	Necrotizing fasciitis	Discontinue Avastin
Hemorrhage	Grade 3 or 4	Discontinue Avastin
Hemorrhage	Recent history of hemoptysis of 1/2 teaspoon (2.5 mL) or more	Withhold Avastin
Thromboembolic Events	Arterial thromboembolism, severe	Discontinue Avastin
Thromboembolic Events	Venous thromboembolism, Grade 4	Discontinue Avastin
Hypertension	Hypertensive crisis Hypertensive encephalopathy	Discontinue Avastin
Hypertension	Hypertension, severe	Withhold Avastin if not controlled with medical management; resume once controlled
Posterior Reversible Encephalopathy Syndrome (PRES)	Any	Discontinue Avastin
Renal Toxicity and Proteinuria	Nephrotic syndrome	Discontinue Avastin
Renal Toxicity and Proteinuria	Proteinuria greater than or equal to 2 grams per 24 hours in absence of nephrotic syndrome	Withhold Avastin until proteinuria less than 2 grams per 24 hours
Infusion-Related Reaction	Severe	Discontinue Avastin
	Clinically significant	Interrupt infusion; resume at a decreased rate of infusion after symptoms resolve
	Mild, clinically insignificant	Decrease infusion rate
Congestive Heart Failure	Any	Discontinue Avastin

View dose and duration information by specific cancer type

Indications

Stage III or IV ovarian cancer (OC) after primary surgery
Avastin, in combination with carboplatin and paclitaxel, followed by Avastin as a single agent, is indicated for the treatment of patients with stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer following initial surgical resection.

Avastin, in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan, is indicated for the treatment of patients with platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who received no more than 2 prior chemotherapy regimens.

Avastin, in combination with carboplatin and paclitaxel, or with carboplatin and gemcitabine, followed by Avastin as a single agent, is indicated for the treatment of patients with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Persistent, recurrent, or metastatic cervical cancer (CC)
Avastin, in combination with paclitaxel and cisplatin or paclitaxel and topotecan, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer.

Metastatic renal cell carcinoma (mRCC)
Avastin, in combination with interferon alfa, is indicated for the treatment of metastatic renal cell carcinoma.

Recurrent glioblastoma (rGBM)
Avastin is indicated for the treatment of recurrent glioblastoma in adults.

First-line non-squamous non-small cell lung cancer (NSCLC)
Avastin, in combination with carboplatin and paclitaxel, is indicated for the first‑line treatment of patients with unresectable, locally advanced, recurrent or metastatic non–squamous non–small cell lung cancer.

Metastatic colorectal cancer (MCRC)
Avastin, in combination with intravenous fluorouracil-based chemotherapy, is indicated for the first‑ or second‑line treatment of patients with metastatic colorectal cancer.

Avastin, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy, is indicated for the second-line treatment of patients with metastatic colorectal cancer who have progressed on a first-line bevacizumab product-containing regimen.

Limitation of Use: Avastin is not indicated for adjuvant treatment of colon cancer.

Hepatocellular carcinoma (HCC)
Avastin, in combination with atezolizumab, is indicated for the treatment of patients with unresectable or metastatic hepatocellular carcinoma who have not received prior systemic therapy.

Serious adverse reactions (Warnings and Precautions)

Serious and sometimes fatal adverse reactions with increased incidence in the Avastin-treated arm vs chemotherapy arm included:
- Gastrointestinal (GI) perforation ranged from 0.3% to 3% of patients across clinical studies
- Non-GI fistulae (<1% to 1.8%, highest in patients with cervical cancer)
- Arterial thromboembolic events (Grade ≥3, 5%, highest in patients with GBM)
- The incidence of wound healing and surgical complications, including serious and fatal complications, is increased in Avastin-treated patients
- Hemorrhage (Grade 3–5) ranged from 0.4% to 7% of patients across clinical studies
- Renal injury and proteinuria
  - Grade 3–4 proteinuria ranged from 0.7% to 7% in clinical studies
  - Nephrotic syndrome (<1%)
Additional serious adverse reactions with increased incidence in the Avastin-treated arm vs chemotherapy arm included:
- Venous thromboembolism (Grade ≥3, 11% seen in GOG-0240)
- Hypertension (Grade 3–4, 5%–18%)
- Posterior reversible encephalopathy syndrome (PRES) (<0.5%)
- Congestive heart failure (CHF): Grade ≥3 left ventricular dysfunction (1%)
Infusion-related reactions with the first dose of Avastin occurred in <3% of patients, and severe reactions occurred in 0.4% of patients
Avoid use in patients with ovarian cancer who have evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction
Inform females of reproductive potential of the risk of ovarian failure prior to initiating treatment with Avastin
An evaluation for the presence of varices is recommended within 6 months of initiation of Avastin in patients with HCC

Pregnancy warning

Based on the mechanism of action and animal studies, Avastin may cause fetal harm
Advise female patients that Avastin may cause fetal harm, and to inform their healthcare provider of a known or suspected pregnancy
Advise females of reproductive potential to use effective contraception during treatment with Avastin and for 6 months after the last dose of Avastin
Advise nursing women not to breastfeed during treatment with Avastin and for 6 months following their last dose of treatment
Avastin may impair fertility

Most common adverse reactions

Across studies, the most common adverse reactions observed in Avastin patients at a rate >10% were:
- Epistaxis
- Headache
- Hypertension
- Rhinitis
- Proteinuria
- Taste alteration
- Dry skin
- Hemorrhage
- Lacrimation disorder
- Back pain
- Exfoliative dermatitis
Across all studies, Avastin was discontinued in 8% to 22% of patients because of adverse reactions

Indication-specific adverse reactions

In Stage III or IV OC after primary surgery, 608 patients received CP+Avastin→Avastin, 607 patients received CP+Avastin→PBO, and 602 patients received CP+PBO→PBO. Grade 3–4 adverse reactions occurring at a higher incidence (≥2%) in either of the Avastin arms vs the chemotherapy only arm were fatigue (CP+Avastin→Avastin, 9%; CP+Avastin→PBO, 6%; CP+PBO→PBO, 6%), hypertension (CP+Avastin→Avastin, 10%; CP+Avastin→PBO, 6%; CP+PBO→PBO, 2%), platelet count decreased (CP+Avastin→Avastin, 21%; CP+Avastin→PBO, 20%; CP+PBO→PBO, 15%), and white blood cell count decreased (CP+Avastin→Avastin, 51%; CP+Avastin→PBO, 53%; CP+PBO→PBO, 50%)

In psOC, Grade 3 or 4 adverse reactions in the OCEANS study occurring at a higher incidence (≥2%) in 247 patients receiving Avastin plus carboplatin and gemcitabine (chemotherapy), compared to 233 patients receiving placebo plus chemotherapy, were thrombocytopenia (40% vs 34%), nausea (4% vs 1.3%), fatigue (6% vs 4%), headache (4% vs 0.9%), proteinuria (10% vs 0.4%), dyspnea (4% vs 1.7%), epistaxis (5% vs 0.4%), and hypertension (17% vs 0.9%)

In psOC, Grade 3 or 4 adverse reactions in the GOG-0213 study occurring at a higher incidence (≥2%) in 325 patients receiving Avastin plus carboplatin and paclitaxel (chemotherapy), compared to 332 patients receiving chemotherapy alone, were hypertension (11% vs 0.6%), fatigue (8% vs 3%), febrile neutropenia (6% vs 3%), proteinuria (8% vs 0%), abdominal pain (6% vs 0.9%), hyponatremia (4% vs 0.9%), headache (3% vs 0.9%), and pain in extremity (3.4% vs 0%)

In prOC, Grade 3–4 adverse reactions in AURELIA occurring at a higher incidence (≥2%) in 179 patients receiving Avastin plus chemotherapy, compared to 181 patients receiving chemotherapy alone, were hypertension (6.7% vs 1.1%) and palmar-plantar erythrodysaesthesia syndrome (4.5% vs 1.7%)

In CC, Grade 3 or 4 adverse reactions in Study GOG-0240, occurring at a higher incidence (≥2%) in 218 patients receiving Avastin plus chemotherapy compared to 222 patients receiving chemotherapy alone, were abdominal pain (12% vs 10%), diarrhea (6% vs 3%), anal fistula (4% vs 0%), proctalgia (3% vs 0%), urinary tract infection (8% vs 6%), cellulitis (3% vs 0.5%), fatigue (14% vs 10%), hypertension (11% vs 0.5%), thrombosis (8% vs 3%), hypokalemia (7% vs 4%), hyponatremia (4% vs 1%), dehydration (4% vs 0.5%), neutropenia (8% vs 4%), lymphopenia (6% vs 3%), back pain (6% vs 3%), and pelvic pain (6% vs 1%)

In mRCC, the most common Grade 3–5 adverse reactions in AVOREN, occurring at a >2% higher incidence in Avastin-treated patients vs controls, were fatigue (13% vs 8%), asthenia (10% vs 7%), proteinuria (7% vs 0%), hypertension (6% vs 1%, including hypertension and hypertensive crisis), and hemorrhage (3% vs 0.3%; including epistaxis, small intestinal hemorrhage, aneurysm ruptured, gastric ulcer hemorrhage, gingival bleeding, hemoptysis, hemorrhage intracranial, large intestinal hemorrhage, respiratory tract hemorrhage, and traumatic hematoma)

In rGBM Study EORTC 26101, the incidence of Grade 3–4 VTE was 5% in patients receiving Avastin with chemotherapy compared to 2% in patients receiving chemotherapy alone. In this study, 22% of patients discontinued treatment in the Avastin with lomustine arm due to adverse reactions compared with 10% of patients in the lomustine arm. In patients receiving Avastin with lomustine, the adverse reaction profile was similar to that observed in other approved indications

In NSCLC, Grade 3–5 (nonhematologic) and Grade 4–5 (hematologic) adverse reactions in Study E4599 occurring at a ≥2% higher incidence in Avastin-treated patients vs controls were neutropenia (27% vs 17%), fatigue (16% vs 13%), hypertension (8% vs 0.7%), infection without neutropenia (7% vs 3%), venous thromboembolism (5% vs 3%), febrile neutropenia (5% vs 2%), pneumonitis/pulmonary infiltrates (5% vs 3%), infection with Grade 3 or 4 neutropenia (4% vs 2%), hyponatremia (4% vs 1%), headache (3% vs 1%), and proteinuria (3% vs 0%)

In first-line MCRC, the most common Grade 3–4 reactions in Study 2107, which occurred at a ≥2% higher incidence in the Avastin plus IFL vs IFL groups, were asthenia (10% vs 7%), abdominal pain (8% vs 5%), pain (8% vs 5%), hypertension (12% vs 2%), deep vein thrombosis (9% vs 5%), intra-abdominal thrombosis (3% vs 1%), syncope (3% vs 1%), diarrhea (34% vs 25%), constipation (4% vs 2%), leukopenia (37% vs 31%), and neutropenia (21% vs 14%)

In second-line MCRC, the most common Grade 3–5 (nonhematologic) and 4–5 (hematologic) reactions in Study E3200, which occurred at a higher incidence (≥2%) in the Avastin plus FOLFOX4 vs FOLFOX4 groups, were fatigue (19% vs 13%), diarrhea (18% vs 13%), sensory neuropathy (17% vs 9%), nausea (12% vs 5%), vomiting (11% vs 4%), dehydration (10% vs 5%), hypertension (9% vs 2%), abdominal pain (8% vs 5%), hemorrhage (5% vs 1%), other neurological (5% vs 3%), ileus (4% vs 1%), and headache (3% vs 0%). These data are likely to underestimate the true adverse event rates due to the reporting mechanisms used in this study

When continued beyond first progression in MCRC, no new safety signals were observed in the TML study (ML18147) when Avastin was administered in second-line MCRC patients who progressed on an Avastin containing regimen in first-line MCRC. The safety data was consistent with the known safety profile established in first- and second-line MCRC

In HCC Study IMbrave150, fatal adverse reactions occurred in 4.6% of patients in the Avastin and atezolizumab arm. The most common adverse reactions leading to death were gastrointestinal and esophageal varices hemorrhage (1.2%) and infections (1.2%). Serious adverse reactions occurred in 38% of patients in the Avastin and atezolizumab arm. The most frequent serious adverse reactions (≥2%) were gastrointestinal hemorrhage (7%), infections (6%), and pyrexia (2.1%). Adverse reactions leading to discontinuation of Avastin occurred in 15% of patients in the Avastin and atezolizumab arm. The most common adverse reactions leading to Avastin discontinuation were hemorrhages (4.9%), including bleeding varicose vein, hemorrhage and gastrointestinal, subarachnoid, and pulmonary hemorrhages; and increased transaminases or bilirubin (0.9%). Adverse reactions leading to interruption of Avastin occurred in 46% of patients in the Avastin and atezolizumab arm; the most common (≥2%) were proteinuria (6%); infections (6%); hypertension (6%); liver function laboratory abnormalities including increased transaminases, bilirubin, or alkaline phosphatase (4.6%); gastrointestinal hemorrhages (3%); thrombocytopenia/decreased platelet count (4.3%); and pyrexia (2.4%)

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch.
You may also report side effects to Genentech at (888) 835-2555.

Please see full Prescribing Information for additional important safety information.

- Avastin Prescribing Information. Genentech, Inc. 2022.
  
  Avastin Prescribing Information. Genentech, Inc. 2022.
- Hurwitz H, Fehrenbacher L, Novotny W, et al. N Engl J Med. 2004;350:2335-2342. PMID: 15175435
  
  Hurwitz H, Fehrenbacher L, Novotny W, et al. N Engl J Med. 2004;350:2335-2342. PMID: 15175435
- Data on file. Genentech, Inc.
  
  Data on file. Genentech, Inc.
- Bennouna J, Sastre J, Arnold D, et al. Lancet Oncol. 2013;14:29-37.
  
  Bennouna J, Sastre J, Arnold D, et al. Lancet Oncol. 2013;14:29-37.
- Österlund P, Alonso-Orduña V, Schlichting C, et al. Poster presented at: European Society for Medical Oncology Meeting; September 28-October 2, 2012; Vienna, Austria.
  
  Österlund P, Alonso-Orduña V, Schlichting C, et al. Poster presented at: European Society for Medical Oncology Meeting; September 28-October 2, 2012; Vienna, Austria.
- Giantonio BJ, Catalano PJ, Meropol NJ, et al. J Clin Oncol. 2007;25:1539-1544. PMID: 17442997
  
  Giantonio BJ, Catalano PJ, Meropol NJ, et al. J Clin Oncol. 2007;25:1539-1544. PMID: 17442997
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer V.2.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 24, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.
  
  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer V.2.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 24, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.
- Sandler A, Gray R, Perry MC, et al. N Engl J Med. 2006;355:2542-2550. PMID: 17167137
  
  Sandler A, Gray R, Perry MC, et al. N Engl J Med. 2006;355:2542-2550. PMID: 17167137
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.5.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 24, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.
  
  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.5.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 24, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.
- Sandler AB, Schiller JH, Gray R, et al. J Clin Oncol. 2009;27:1405-1412.
  
  Sandler AB, Schiller JH, Gray R, et al. J Clin Oncol. 2009;27:1405-1412.
- Cohen MH, Gootenberg J, Keegan P, Pazdur R. Oncologist. 2007;12:713-718.
  
  Cohen MH, Gootenberg J, Keegan P, Pazdur R. Oncologist. 2007;12:713-718.
- Sandler A, Leon L, Fages S, et al. Poster presented at: World Conference on Lung Cancer; July 3-7, 2011; Amsterdam, The Netherlands.
  
  Sandler A, Leon L, Fages S, et al. Poster presented at: World Conference on Lung Cancer; July 3-7, 2011; Amsterdam, The Netherlands.
- Escudier B, Bellmunt J, Negrier S, et al. Slides presented at: Annual Meeting of the American Society of Clinical Oncology; May 29-June 2, 2009; Orlando, FL.
  
  Escudier B, Bellmunt J, Negrier S, et al. Slides presented at: Annual Meeting of the American Society of Clinical Oncology; May 29-June 2, 2009; Orlando, FL.
- Escudier B, Pluzanska A, Koralewski P, et al. Lancet. 2007;370:2103-2111. PMID: 18156031
  
  Escudier B, Pluzanska A, Koralewski P, et al. Lancet. 2007;370:2103-2111. PMID: 18156031
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Kidney Cancer V.1.2020. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 24, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.
  
  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Kidney Cancer V.1.2020. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 24, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.
- Tewari KS, Sill MW, Long HJ III, et al. N Engl J Med. 2014;370:734-743 [supplementary appendix appears online].
  
  Tewari KS, Sill MW, Long HJ III, et al. N Engl J Med. 2014;370:734-743 [supplementary appendix appears online].
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Cervical Cancer V.4.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 25, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.
  
  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Cervical Cancer V.4.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 25, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.
- Rich JT, Neely JG, Paniello RC, et al. Otolaryngol Head Neck Surg. 2010;143:331-336.
  
  Rich JT, Neely JG, Paniello RC, et al. Otolaryngol Head Neck Surg. 2010;143:331-336.
- Burger RA, Brady MF, Bookman MA, et al. N Engl J Med. 2011;365:2473-2483.
  
  Burger RA, Brady MF, Bookman MA, et al. N Engl J Med. 2011;365:2473-2483.
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Ovarian Cancer V.1.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 24, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.
  
  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Ovarian Cancer V.1.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 24, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.
- Aghajanian C, Blank S, Goff B, et al. J Clin Oncol. 2012;30(17):2039-2045.
  
  Aghajanian C, Blank S, Goff B, et al. J Clin Oncol. 2012;30(17):2039-2045.
- Aghajanian C, Goff B, Nycum LR, et al. Gynecol Oncol. 2015;139(1):10-16.
  
  Aghajanian C, Goff B, Nycum LR, et al. Gynecol Oncol. 2015;139(1):10-16.
- Coleman RL, Brady MF, Herzog TJ, et al. Lancet Oncol. 2013;18(6):779-791.
  
  Coleman RL, Brady MF, Herzog TJ, et al. Lancet Oncol. 2013;18(6):779-791.
- Pujade-Lauraine E, Hilpert F, Weber B, et al. J Clin Oncol. 2014;32(13):1302-1308.
  
  Pujade-Lauraine E, Hilpert F, Weber B, et al. J Clin Oncol. 2014;32(13):1302-1308.
- Bevacizumab and lomustine for recurrent GBM. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01290939. Updated February 21, 2018. Accessed July 24, 2019.
  
  Bevacizumab and lomustine for recurrent GBM. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01290939. Updated February 21, 2018. Accessed July 24, 2019.
- Friedman HS, Prados MD, Wen PY, et al. J Clin Oncol. 2009;27:4733-4740.
  
  Friedman HS, Prados MD, Wen PY, et al. J Clin Oncol. 2009;27:4733-4740.
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Central Nervous System Cancers V.1.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 24, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.
  
  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Central Nervous System Cancers V.1.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 24, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.
- Hicklin DJ, Ellis LM. J Clin Oncol. 2005;23:1011-1027.
  
  Hicklin DJ, Ellis LM. J Clin Oncol. 2005;23:1011-1027.
- Bergers G, Benjamin LE. Nat Rev Cancer. 2003;3:401-410.
  
  Bergers G, Benjamin LE. Nat Rev Cancer. 2003;3:401-410.
- Folkman J. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: Principles & Practice of Oncology. Vol 2. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:2865-2882.
  
  Folkman J. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: Principles & Practice of Oncology. Vol 2. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:2865-2882.
- Hanrahan V, Currie MJ, Gunningham SP, et al. J Pathol. 2003;200:183-194.
  
  Hanrahan V, Currie MJ, Gunningham SP, et al. J Pathol. 2003;200:183-194.
- Rini BI, Small EJ. J Clin Oncol. 2005;23:1028-1043.
  
  Rini BI, Small EJ. J Clin Oncol. 2005;23:1028-1043.
- Presta LG, Chen H, O’Connor SJ, et al. Cancer Res. 1997;57:4593-4599.
  
  Presta LG, Chen H, O’Connor SJ, et al. Cancer Res. 1997;57:4593-4599.
- Ferrara N. Endocr Rev. 2004;25:581-611.
  
  Ferrara N. Endocr Rev. 2004;25:581-611.
- Ferrara N, Hillan KJ, Gerber HP, et al. Nat Rev Drug Discov. 2004;3:391-400.
  
  Ferrara N, Hillan KJ, Gerber HP, et al. Nat Rev Drug Discov. 2004;3:391-400.
- O’Connor JPB, Carano RAD, Clamp AR, et al. Clin Cancer Res. 2009;15:6674-6682.
  
  O’Connor JPB, Carano RAD, Clamp AR, et al. Clin Cancer Res. 2009;15:6674-6682.
- Tobelem G. Targ Oncol. 2007;2:153-164.
  
  Tobelem G. Targ Oncol. 2007;2:153-164.
- Yuan F, Chen Y, Dellian M, et al. Proc Natl Acad Sci U S A. 1996;93:14765-14770.
  
  Yuan F, Chen Y, Dellian M, et al. Proc Natl Acad Sci U S A. 1996;93:14765-14770.
- Willett CG, Boucher Y, di Tomaso E, et al. Nat Med. 2004;10:145-147.
  
  Willett CG, Boucher Y, di Tomaso E, et al. Nat Med. 2004;10:145-147.
- Lee CG, Heijn M, di Tomaso E, et al. Cancer Res. 2000;60:5565-5570.
  
  Lee CG, Heijn M, di Tomaso E, et al. Cancer Res. 2000;60:5565-5570.
- Gerber HP, Ferrara N. Cancer Res. 2005;65:671-680.
  
  Gerber HP, Ferrara N. Cancer Res. 2005;65:671-680.
- Yanagisawa M, Yorozu K, Kurasawa M, et al. Anti-Cancer Drugs. 2010;21:687-694.
  
  Yanagisawa M, Yorozu K, Kurasawa M, et al. Anti-Cancer Drugs. 2010;21:687-694.
- Borgström P, Hillan KJ, Sriramarao P, et al. Cancer Res. 1996;56:4032-4039.
  
  Borgström P, Hillan KJ, Sriramarao P, et al. Cancer Res. 1996;56:4032-4039.
- Borgström P, Bourdon MA, Hillan KJ, et al. Prostate. 1998;35:1-10.
  
  Borgström P, Bourdon MA, Hillan KJ, et al. Prostate. 1998;35:1-10.
- Bagri A, Berry L, Gunter B, et al. Clin Cancer Res. 2010;16:3887-3900 [and supplemental appendix].
  
  Bagri A, Berry L, Gunter B, et al. Clin Cancer Res. 2010;16:3887-3900 [and supplemental appendix].
- Warren RS, Yuan H, Matli MR, et al. J Clin Invest. 1995;95:1789-1797.
  
  Warren RS, Yuan H, Matli MR, et al. J Clin Invest. 1995;95:1789-1797.
- Mabuchi S, Terai Y, Morishige K, et al. Clin Cancer Res. 2008;14:7781-7789.
  
  Mabuchi S, Terai Y, Morishige K, et al. Clin Cancer Res. 2008;14:7781-7789.
- Nagy JA, Dvorak AM, Dvorak HF. Annu Rev Pathol. 2007;2:251-275.
  
  Nagy JA, Dvorak AM, Dvorak HF. Annu Rev Pathol. 2007;2:251-275.
- Galizia G, Lieto E, Ferraraccio F, et al. Clin Cancer Res. 2004;10:3490-3499.
  
  Galizia G, Lieto E, Ferraraccio F, et al. Clin Cancer Res. 2004;10:3490-3499.
- Vosseler S, Mirancea N, Bohlen P, et al. Cancer Res. 2005;65:1294-1305.
  
  Vosseler S, Mirancea N, Bohlen P, et al. Cancer Res. 2005;65:1294-1305.
- MMIT Analysis.
  
  MMIT Analysis.
- IQVIA Plantrak Corticosteroid Data.
  
  IQVIA Plantrak Corticosteroid Data.
- HLI lives database.
  
  HLI lives database.