Skip To Main Content

Ovarian Cancer: Avastin Safety Profile

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.

Recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer (rOC)
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. 

Avastin has a well-documented safety profile

Grade 1–5 adverse reactions occurring at a higher incidence (≥5%) in patients receiving Avastin with chemotherapy followed by single-agent Avastin vs chemotherapy alone in the GOG-0218 study[1] 

Adverse reaction* CP + Avastin→Avastin
(%)
(n=608)
CP + Avastin→PBO
(%)
(n=607)
CP + PBO→PBO
(%)
(n=602)
Gastrointestinal disorders
Diarrhea 38 40 34
Nausea 58 53 51
Stomatitis 25 19 14
General disorders and administration site conditions
Fatigue 80 72 73
Musculoskeletal and connective tissue disorders
Arthralgia 41 33 35
Muscular weakness 15 13 9
Pain in extremity 25 19 17
Nervous system disorders
Dysarthria 12 10 2
Headache 34 26 21
Respiratory, thoracic, and mediastinal disorders
Dyspnea 26 28 20
Epistaxis 31 30 9
Nasal mucosal disorder 10 7 4
Vascular disorders
Hypertension 32 24 14

GOG=Gynecologic Oncology Group; CP=carboplatin + paclitaxel; PBO=placebo; AUC=area under the curve; q3w=every 3 weeks.
The demographics of the safety population were similar to the demographics of the efficacy population.
CP+Avastin→Avastin=carboplatin (AUC 6) and paclitaxel (175 mg/m2) for 6 cycles, with concurrent Avastin started at cycle 2, followed by single-agent Avastin q3w for a total of up to 22 cycles of therapy.
CP+Avastin→PBO=carboplatin (AUC 6) and paclitaxel (175 mg/m2) for 6 cycles, with concurrent Avastin started at cycle 2, followed by placebo alone q3w for a total of up to 22 cycles of therapy.
CP+PBO→PBO=carboplatin (AUC 6) and paclitaxel (175 mg/m2) for 6 cycles, with concurrent placebo started at cycle 2, followed by placebo alone q3w for a total of up to 22 cycles of therapy.
*National Cancer Institute Common Terminology Criteria version 3.

  • 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%)[1]
  • No grade 5 adverse events occurred at a higher incidence of ≥3% in the CP+Avastin→Avastin and CP+Avastin→PBO arms vs the CP+PBO→PBO arm[19] 

Safety profile of Avastin in psOC was evaluated in the OCEANS study: Avastin plus chemotherapy vs placebo plus chemotherapy[1]

Grade 1−5 adverse events in OCEANS occurring at higher incidence (≥5%) in Avastin plus chemotherapy vs placebo + chemotherapy 

Adverse event Avastin + carboplatin and gemcitabine (%)
(n=247)
Placebo + carboplatin and gemcitabine (%)
(n=233)
Blood and lymphatic system disorders
Thrombocytopenia 58 51
Gastrointestinal disorders
Nausea 72 66
Diarrhea 38 29
Stomatitis 15 7
Hemorrhoids 8 3
Gingival bleeding 7 0
General disorders and administration site conditions
Fatigue 82 75
Mucosal inflammation 15 10
Infections and infestations
Sinusitis 15 9
Injury, poisoning, and procedural complications
Contusion 17 9
Musculoskeletal and connective tissue disorders
Arthralgia 28 19
Back pain 21 13
Nervous system disorders
Headache 49 30
Dizziness 23 17
Psychiatric disorders
Insomnia 21 15
Renal and urinary disorders
Proteinuria 20 3
Respiratory, thoracic, and mediastinal disorders
Epistaxis 55 14
Dyspnea 30 24
Cough 26 18
Oropharyngeal pain 16 10
Dysphonia 13 3
Rhinorrhea 10 4
Sinus congestion 8 2
Vascular disorders
Hypertension 42 9

psOC=platinum-sensitive ovarian cancer.

  • There were no grade 5 events occurring at a higher incidence (≥3%) in patients receiving Avastin plus chemotherapy vs placebo plus chemotherapy[21,22]
  • Grade 3 or 4 adverse reactions 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%)[1]

Safety profile of Avastin in psOC was evaluated in the GOG-0213 study: Avastin plus chemotherapy vs chemotherapy alone[1]

Grade 1–5 adverse events in GOG-0213 occurring at higher incidence (≥5%) in Avastin plus chemotherapy vs chemotherapy alone 

Adverse event Avastin + carboplatin and paclitaxel (%)
(n=325)
Carboplatin and paclitaxel alone (%)
(n=332)
Gastrointestinal disorders
Diarrhea 39 32
Abdominal pain 33 28
Vomiting 33 25
Stomatitis 33 16
Metabolism and nutrition disorders
Decreased appetite 35 25
Hyperglycemia 31 24
Hypomagnesemia 27 17
Hyponatremia 17 6
Hypocalcemia 12 5
Hypoalbuminemia 11 6
Hyperkalemia 9 3
Musculoskeletal and connective tissue disorders
Arthralgia 45 30
Myalgia 29 18
Pain in extremity 25 14
Back pain 17 10
Muscular weakness 13 8
Neck pain 9 0
Respiratory, thoracic, and mediastinal disorders
Epistaxis 33 2
Dyspnea 30 25
Cough 30 17
Rhinitis allergic 17 4
Nasal mucosal disorder 14 3
Nervous system disorders
Headache 38 20
Dysarthria 14 2
Dizziness 13 8
Investigations
Aspartate aminotransferase increased 15 9
Weight decreased 15 4
Blood creatinine increased 13 5
Skin and subcutaneous tissue disorders
Exfoliative rash 23 16
Nail disorder 10 2
Dry skin 7 2
Vascular disorders
Hypertension 42 3
Renal and urinary disorders
Proteinuria 17 1
General disorders and administration site conditions
Chest pain 8 2
Infections and infestations
Sinusitis 7 2
  • There were no grade 5 events occurring at a higher incidence (≥3%) in patients receiving Avastin plus chemotherapy vs chemotherapy alone[3,23]
  • Grade 3 or 4 adverse events 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%)[1] 

Safety profile of Avastin in prOC was evaluated in the AURELIA study: Avastin plus chemotherapy vs chemotherapy alone[1]

Grade 3–4 adverse events observed in the AURELIA study with ≥2% higher incidence in the Avastin plus chemotherapy* arm 

Adverse event Avastin + chemotherapy (%)
(n=179)
Chemotherapy alone (%)
(n=181)
Hypertension 6.7 1.1
Palmar-plantar erythrodysesthesia syndrome 4.5 1.7

prOC=platinum-resistant ovarian cancer.
*Chemotherapy included paclitaxel, pegylated liposomal doxorubicin, or topotecan.

There were no grade 5 events occurring at a higher incidence (≥3%) in patients receiving Avastin plus chemotherapy vs chemotherapy alone.[24]

Grade 2–4 adverse events observed in the AURELIA study with ≥5% higher incidence in the Avastin plus chemotherapy arm[1,22] 

Adverse event Avastin + chemotherapy (%)
(n=179)
Chemotherapy alone (%)
(n=181)
Blood and lymphatic system disorders
Neutropenia 30.7 25.4
General disorders and administration site conditions
Mucosal inflammation 12.8 5.5
Infections and infestations
Infection 10.6 4.4
Nervous system disorders
Peripheral sensory neuropathy 17.9 7.2
Renal and urinary disorders
Proteinuria 12.3 0.6
Respiratory, thoracic, and mediastinal disorders
Epistaxis 5.0 0
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome 10.6 5.0
Vascular disorders
Hypertension 19.0 5.5

Chemotherapy included paclitaxel, pegylated liposomal doxorubicin, or topotecan. 

Indication

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.

Recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer (rOC)
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.

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%)

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. 2020.

      Avastin Prescribing Information. Genentech, Inc. 2020.

    • 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.