Impact of G-CSF Prophylaxis on Chemotherapy Dose-Intensity, Link Between Dose-Intensity and Survival in Patients with Metastatic Pancreatic Adenocarcinoma

Overview

Journal Oncologist

Publisher Oxford University Press

Specialty Oncology

Date 2022 Mar 15

PMID 35289915

Authors

Clemence Canton

Olayide Boussari

Mathieu Boulin

Karine Le Malicot

Julien Taieb

Laetitia Dahan

Anthony Lopez

Come Lepage

Jean-Baptiste Bachet

Affiliations

Soon will be listed here.

Abstract

Background: In metastatic pancreatic adenocarcinoma, few data are available on the use of granulocyte-colony stimulating factor (G-CSF) prophylaxis and its impact on dose-intensity (DI), or the link between DI and progression-free survival (PFS). This study assessed the impact of G-CSF prophylaxis on the DI received by patients and the relationship between full DI and PFS according to chemotherapy regimens.

Patients And Methods: Patients from three first-line randomized phase II clinical trials were included in this retrospective cohort. G-CSF prophylaxis groups were identified and balanced according to baseline characteristics using a propensity score. Patients were classified into 2 treatment groups (FOLFIRINOX vs FOLFIRI/nab-paclitaxel (NAB)). DI was a binary variable (full/reduced). Adverse events were defined using NCI-CTCAE v4.0.

Results: Of the 498 patients, 154 (31%) were in "prophylaxis" group; 179 (36%) were treated by FOLFIRINOX and 319 (64%) by FOLFIRI/NAB. In FOLFIRINOX group, G-CSF prophylaxis was significantly associated with a higher rate of full DI (OR, 5.07; 95% CI, 1.52-16.90; P < .01) while in FOLFIRI/NAB group, it was significantly associated with a lower rate of full DI (OR, 0.23; 95% CI, 0.06-0.83; P = .03). Full DI was associated with a non-significant increase in PFS (FOLFIRINOX group: HR 0.83; 95% CI, 0.59-1.16; P = .27; FOLFIRI/NAB group: HR 0.84; 95% CI, 0.63-1.11; P = .22).

Conclusion: Granulocyte-colony stimulating factor prophylaxis was associated with a higher rate of full DI with FOLFIRINOX. Full DI was associated with a non-significant increase in PFS. These results need to be confirmed prospectively.

Citing Articles

Optimal use of granulocyte colony-stimulating factor prophylaxis to improve survival in cancer patients receiving treatment : An expert view.

Gascon P, Awada A, Karihtala P, Lorenzen S, Minichsdorfer C Wien Klin Wochenschr. 2023; 136(11-12):362-368.

PMID: 38010512 PMC: 11156747. DOI: 10.1007/s00508-023-02300-6.

G-CSF rescue of FOLFIRINOX-induced neutropenia leads to systemic immune suppression in mice and humans.

Cardot-Ruffino V, Bollenrucher N, Delius L, Wang S, Brais L, Remland J J Immunother Cancer. 2023; 11(6).

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References

Guo J, Wu M, Guo L, Zuo Q . Pretreatment blood neutrophil/lymphocyte ratio is associated with metastasis and predicts survival in patients with pancreatic cancer. Bull Cancer. 2018; 105(2):146-154. DOI: 10.1016/j.bulcan.2017.10.028. View

Klastersky J, de Naurois J, Rolston K, Rapoport B, Maschmeyer G, Aapro M . Management of febrile neutropaenia: ESMO Clinical Practice Guidelines. Ann Oncol. 2016; 27(suppl 5):v111-v118. DOI: 10.1093/annonc/mdw325. View

Smith T, Khatcheressian J, Lyman G, Ozer H, Armitage J, Balducci L . 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol. 2006; 24(19):3187-205. DOI: 10.1200/JCO.2006.06.4451. View

Ninomiya R, Nakazawa A, Miyata Y, Mitsui T, Komagome M, Maki A . [Primary Prophylactic Administration of Pegfilgrastim in FOLFIRINOX Therapy for Locally Advanced Pancreatic Carcinoma]. Gan To Kagaku Ryoho. 2017; 43(12):1678-1680. View

Chen P, Lei J, Wu Y, Zhou B . Pegylated G-CSF Combined with mFOLFIRINOX for Advanced Pancreatic Cancer Patients. Intern Med. 2019; 59(6):877. PMC: 7118392. DOI: 10.2169/internalmedicine.3790-19. View

Bohlius J, Herbst C, Reiser M, Schwarzer G, Engert A . Granulopoiesis-stimulating factors to prevent adverse effects in the treatment of malignant lymphoma. Cochrane Database Syst Rev. 2008; (4):CD003189. PMC: 7144686. DOI: 10.1002/14651858.CD003189.pub4. View

Bosly A, Bron D, Van Hoof A, De Bock R, Berneman Z, Ferrant A . Achievement of optimal average relative dose intensity and correlation with survival in diffuse large B-cell lymphoma patients treated with CHOP. Ann Hematol. 2007; 87(4):277-83. DOI: 10.1007/s00277-007-0399-y. View

Burris 3rd H, Moore M, Andersen J, Green M, Rothenberg M, Modiano M . Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997; 15(6):2403-13. DOI: 10.1200/JCO.1997.15.6.2403. View

Smith T, Bohlke K, Lyman G, Carson K, Crawford J, Cross S . Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2015; 33(28):3199-212. DOI: 10.1200/JCO.2015.62.3488. View

10.

Dahan L, Williet N, Le Malicot K, Phelip J, Desrame J, Bouche O . Randomized Phase II Trial Evaluating Two Sequential Treatments in First Line of Metastatic Pancreatic Cancer: Results of the PANOPTIMOX-PRODIGE 35 Trial. J Clin Oncol. 2021; 39(29):3242-3250. DOI: 10.1200/JCO.20.03329. View

11.

Austin P . A Tutorial on Multilevel Survival Analysis: Methods, Models and Applications. Int Stat Rev. 2018; 85(2):185-203. PMC: 5756088. DOI: 10.1111/insr.12214. View

12.

DAgostino Jr R . Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998; 17(19):2265-81. DOI: 10.1002/(sici)1097-0258(19981015)17:19<2265::aid-sim918>3.0.co;2-b. View

13.

Green M, Koelbl H, Baselga J, Galid A, Guillem V, Gascon P . A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy. Ann Oncol. 2002; 14(1):29-35. DOI: 10.1093/annonc/mdg019. View

14.

Pettengell R, Gurney H, Radford J, Deakin D, James R, Wilkinson P . Granulocyte colony-stimulating factor to prevent dose-limiting neutropenia in non-Hodgkin's lymphoma: a randomized controlled trial. Blood. 1992; 80(6):1430-6. View

15.

Leonard R, Mansi J, Keerie C, Yellowlees A, Crawford S, Benstead K . A randomised trial of secondary prophylaxis using granulocyte colony-stimulating factor ('SPROG' trial) for maintaining dose intensity of standard adjuvant chemotherapy for breast cancer by the Anglo-Celtic Cooperative Group and NCRN. Ann Oncol. 2015; 26(12):2437-41. DOI: 10.1093/annonc/mdv389. View

16.

Aapro M, Bohlius J, Cameron D, Dal Lago L, Donnelly J, Kearney N . 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer. 2010; 47(1):8-32. DOI: 10.1016/j.ejca.2010.10.013. View

17.

Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y . FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011; 364(19):1817-25. DOI: 10.1056/NEJMoa1011923. View

18.

Bachet J, Hammel P, Desrame J, Meurisse A, Chibaudel B, Andre T . Nab-paclitaxel plus either gemcitabine or simplified leucovorin and fluorouracil as first-line therapy for metastatic pancreatic adenocarcinoma (AFUGEM GERCOR): a non-comparative, multicentre, open-label, randomised phase 2 trial. Lancet Gastroenterol Hepatol. 2017; 2(5):337-346. DOI: 10.1016/S2468-1253(17)30046-8. View

19.

Sarosy G, Hussain M, Seiden M, Fuller A, Nikrui N, Goodman A . Ten-year follow-up of a phase 2 study of dose-intense paclitaxel with cisplatin and cyclophosphamide as initial therapy for poor-prognosis, advanced-stage epithelial ovarian cancer. Cancer. 2010; 116(6):1476-84. PMC: 2836408. DOI: 10.1002/cncr.24861. View

20.

Lal A, Bhurgri Y, Rizvi N, Virwani M, Memon R, Saeed W . Factors influencing in-hospital length of stay and mortality in cancer patients suffering from febrile neutropenia. Asian Pac J Cancer Prev. 2008; 9(2):303-8. View