Bevacizumab and cyclosphosphamide, doxorubicin, vincristine and prednisone in combination for patients with peripheral T-cell or natural killer cell neoplasms: An Eastern Cooperative Oncology Group study (E2404)

Kristen Ganjoo, Fangxin Hong, Sandra J. Horning, Randy D. Gascoyne, Yasodha Natkunam, Lode J. Swinnen, Thomas Matthew Habermann, Brad S. Kahl, Ranjana H. Advani

Research output: Contribution to journalArticle

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Abstract

Peripheral T-cell lymphoma (PTCL) and natural killer (NK) cell lymphoma have poor survival with conventional cytotoxic chemotherapy. Because angiogenesis plays an important role in the biology of PTCL, a fully humanized anti-vascular endothelial growth factor (VEGF) antibody, bevacizumab (A), was studied in combination with standard cyclosphosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy (ACHOP) to evaluate its potential to improve outcome in these patients. Patients were treated with 6-8 cycles of ACHOP followed by eight doses of maintenance A (15 mg/kg every 21 days). Fortysix patients were enrolled on this phase 2 study from July 2006 through March 2009. Forty-four patients were evaluable for toxicity and 39 were evaluable for response, progression and survival. A total of 324 cycles (range: 2-16, median 7) were administered to 39 evaluable patients and only nine completed all planned treatment. The overall response rate was 90% with 19 (49%) complete response/complete response unconfirmed (CR/CRu) and 16 (41%) a partial response (PR). The 1-year progression-free survival (PFS) rate was 44% at a median followup of 3 years. The median PFS and overall survival (OS) rates were 7.7 and 22 months, respectively. Twenty-three patients died (21 from lymphoma, two while in remission). Grade 3 or 4 toxicities included febrile neutropenia ( n = 8), anemia ( n = 3), thrombocytopenia ( n = 5), congestive heart failure ( n = 4), venous thrombosis ( n = 3), gastrointestinal hemorrhage/ perforation ( n = 2), infection ( n = 8) and fatigue ( n = 6). Despite a high overall response rate, the ACHOP regimen failed to result in durable remissions and was associated with significant toxicities. Studies of novel therapeutics are needed for this patient population, whose clinical outcome remains poor.

Original languageEnglish (US)
Pages (from-to)768-772
Number of pages5
JournalLeukemia and Lymphoma
Volume55
Issue number4
DOIs
StatePublished - 2014

Fingerprint

Vincristine
Prednisone
Natural Killer Cells
Doxorubicin
T-Lymphocytes
Neoplasms
Peripheral T-Cell Lymphoma
Disease-Free Survival
Lymphoma
Survival Rate
Drug Therapy
Febrile Neutropenia
Gastrointestinal Hemorrhage
Survival
Bevacizumab
Venous Thrombosis
Vascular Endothelial Growth Factor A
Fatigue
Anemia
Heart Failure

Keywords

  • Chemotherapeutic approaches
  • Immunotherapeutic approaches
  • Lymphoma and Hodgkin disease

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Bevacizumab and cyclosphosphamide, doxorubicin, vincristine and prednisone in combination for patients with peripheral T-cell or natural killer cell neoplasms : An Eastern Cooperative Oncology Group study (E2404). / Ganjoo, Kristen; Hong, Fangxin; Horning, Sandra J.; Gascoyne, Randy D.; Natkunam, Yasodha; Swinnen, Lode J.; Habermann, Thomas Matthew; Kahl, Brad S.; Advani, Ranjana H.

In: Leukemia and Lymphoma, Vol. 55, No. 4, 2014, p. 768-772.

Research output: Contribution to journalArticle

Ganjoo, Kristen ; Hong, Fangxin ; Horning, Sandra J. ; Gascoyne, Randy D. ; Natkunam, Yasodha ; Swinnen, Lode J. ; Habermann, Thomas Matthew ; Kahl, Brad S. ; Advani, Ranjana H. / Bevacizumab and cyclosphosphamide, doxorubicin, vincristine and prednisone in combination for patients with peripheral T-cell or natural killer cell neoplasms : An Eastern Cooperative Oncology Group study (E2404). In: Leukemia and Lymphoma. 2014 ; Vol. 55, No. 4. pp. 768-772.
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abstract = "Peripheral T-cell lymphoma (PTCL) and natural killer (NK) cell lymphoma have poor survival with conventional cytotoxic chemotherapy. Because angiogenesis plays an important role in the biology of PTCL, a fully humanized anti-vascular endothelial growth factor (VEGF) antibody, bevacizumab (A), was studied in combination with standard cyclosphosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy (ACHOP) to evaluate its potential to improve outcome in these patients. Patients were treated with 6-8 cycles of ACHOP followed by eight doses of maintenance A (15 mg/kg every 21 days). Fortysix patients were enrolled on this phase 2 study from July 2006 through March 2009. Forty-four patients were evaluable for toxicity and 39 were evaluable for response, progression and survival. A total of 324 cycles (range: 2-16, median 7) were administered to 39 evaluable patients and only nine completed all planned treatment. The overall response rate was 90{\%} with 19 (49{\%}) complete response/complete response unconfirmed (CR/CRu) and 16 (41{\%}) a partial response (PR). The 1-year progression-free survival (PFS) rate was 44{\%} at a median followup of 3 years. The median PFS and overall survival (OS) rates were 7.7 and 22 months, respectively. Twenty-three patients died (21 from lymphoma, two while in remission). Grade 3 or 4 toxicities included febrile neutropenia ( n = 8), anemia ( n = 3), thrombocytopenia ( n = 5), congestive heart failure ( n = 4), venous thrombosis ( n = 3), gastrointestinal hemorrhage/ perforation ( n = 2), infection ( n = 8) and fatigue ( n = 6). Despite a high overall response rate, the ACHOP regimen failed to result in durable remissions and was associated with significant toxicities. Studies of novel therapeutics are needed for this patient population, whose clinical outcome remains poor.",
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AU - Hong, Fangxin

AU - Horning, Sandra J.

AU - Gascoyne, Randy D.

AU - Natkunam, Yasodha

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AU - Habermann, Thomas Matthew

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AU - Advani, Ranjana H.

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