Evaluation of the Use of Granulocyte Colony-Stimulating Factors (G-CSFs) for Neutropenia Primary Prophylaxis in Solid Tumors at a Tertiary Care Hospital, Retrospective Study
Received Date: Nov 01, 2017 / Accepted Date: Nov 29, 2017 / Published Date: Dec 06, 2017
Objective: First, to determine the appropriate prescribing of granulocyte colony-stimulating factors (G-CSFs) for febrile neutropenia (FN) as primary prophylaxis during the first cycle of chemotherapy in breast, lung, gastric, esophageal, nasopharyngeal or colorectal cancer patients. Second, to compare the incidence of FN between patients who received G-CSF appropriately and inappropriately.
Methods: This was a retrospective cohort study conducted at the Princess Norah bint Abdulrahman Al Faisal Oncology Center. We used cancer registry report which included adult patients with newly diagnosed solid tumors, such as breast, lung, gastric, esophageal, nasopharyngeal and colorectal cancer between January 2013 and December 2013. Patients were excluded if they did not receive chemotherapy after diagnosis and had renal or liver impairment. The appropriate indication of G-CSFs for FN primary prophylaxis was evaluated based on the National Comprehensive Cancer Network (NCCN) guidelines and published data.
Results: G-CSFs were appropriately prescribed as primary prophylaxis in 85% of patients. The incidence of FN between the appropriate and inappropriate groups were not statistically significant (p=0.315). However, G-CSF use was inappropriate in 28 of the 29 patients who received chemotherapy regimens with high risk of developing FN; among these patients only three patients developed FN.
Conclusion: The prescribing of G-CSFs for FN primary prophylaxis at our institution was found to be inappropriate on some occasions; mostly when G-CSFs were not prescribed with regimens associated with high risk of FN.
Keywords: GCSF; Primary prophylaxis; Solid tumors; Febrile neutropenia; Chemotherapy
Febrile neutropenia (FN) is a serious and life-threatening condition that may increase hospitalization due to fever and potentially fatal infections after chemotherapy [1,2]. The National Comprehensive Cancer Network (NCCN) defines FN as a single oral temperature of ≥ 38.3°C ( ≥ 100.9°F) or sustained 38.0°C ( ≥ 100.4°F) for 1 hour and an absolute neutrophil count of<500 neutrophils/ mm3 or <1000 neutrophils/mm3 with a predicted decline to <500 neutrophils/mm3 over the following 48 h . Medications such as granulocyte colony-stimulating factors (G-CSFs) are used for primary prophylaxis to reduce the incidence of FN in cancer patients during chemotherapy. G-CSFs increase production and activation of neutrophils and then promote their migration [4,5]. Patients with solid cancers, who do not receive prophylactic G-CSFs, exhibit a higher incidence of FN in comparison to patients who receive G-CSFs as part of the chemotherapy regimen [6-9]. NCCN guidelines recommend using primary prophylaxis with G-CSFs in patients undergoing chemotherapy regimen with ≥ 20% risk of developing FN.3 For chemotherapy regimens associated with intermediate-risk of FN (10-20%), NCCN guidelines recommend not to use G-CSFs unless patients display poor renal function, liver dysfunction, advanced age (>65 years), previous chemotherapy with neutropenia, previous radiation therapy with neutropenia, preexisting neutropenia or bone marrow involvement with tumor, previous infection or open wounds, recent surgery, poor performance status or HIV-infection.3 For low-risk FN chemotherapy regimens (<10%), NCCN guidelines recommend not to use G-CSFs . G-CSFs use associated with serious adverse effect like thrombocytopenia and splenic rupture that increase with appropriate use [10,11]. However, previous studies showed an improvement in quality of life and a negligible difference in cost when using or not G-CSFs for primary prophylaxis [12-14]. Moreover, The Federal Drug Administration (FDA) restricted the use of G-CSFs (Eg: Filgrastim) for: no myeloid malignancies, acute myeloid leukemia following induction or consolidation chemotherapy, bone marrow transplantation, hematopoietic radiation injury syndrome, peripheral blood progenitor cell mobilization for collection and therapy for severe chronic neutropenia. For the previous reasons, we evaluated the prescribing pattern of G-CSFs for FN primary prophylaxis during the first cycle of chemotherapy in solid tumors since there is no previous evaluation of G-CSFs utilization in our institution.
This is a retrospective cohort study conducted at the Princess Norah bint Abdulrahman Al Faisal Oncology Center at the King Abdul-Aziz Medical City, Western Region. The study was approved by the King Abdullah International Medical Research Center on September 1, 2015. Between January 2013 and December 2013 entries in the cancer registry included adult patients with newly diagnosed breast, lung and gastric, esophageal, nasopharyngeal and colorectal cancers. Patients were excluded if they did not receive chemotherapy after diagnosis, had renal impairment or liver impairment. The appropriate use of G-CSFs for FN primary prophylaxis was evaluated based on NCCN guidelines and published data.
G-CSFs prescribing were considered appropriate in patients who received chemotherapy regimens associated with high-risk of developing of FN or intermediate risk of FN with comorbidities. FN risks associated with specific chemotherapy regimens were derived from NCCN guidelines and previous studies (Appendix Table 1). Descriptive statistics and Chi-square test were used when summarizing the results for primary and secondary outcomes.
|Chemotherapy regimen||FN risk||Study|
|Doxorubicin+Cyclophosphamide||<10||Nabholtz  Chan |
|Paclitaxel+Carboplatin+Trastuzumab weekly||<10||Perez |
|Paclitaxel+Carboplatin+Trastuzumab q3w||10-20||Perez |
|Docetaxel+Carboplatin+Trastuzumab||10-20||Gilbar  Valero |
|Bevacizumab + Capecitabine||<10||Gligorov |
|Oxaliplatin+Leucovorin+Fluorouracil||<10||Hacibekiroglu  Andre |
|Irinotecan +Leucovorin+Fluorouracil+Bevacizumab||<10||Comella |
|Irinotecan+Capecitabine||<10||Li W |
|Irinotecan Fluorouracil/Leucovorin||<10||Douillard |
|Vinorelbine+Carboplatin||>20||Agelaki  LeCaer |
|Rituximab+Doxorubicin+Vincristine+Cyclophosphamide+Prednisolone every 21 days||10-20||Cunningham |
|Rituximab+Doxorubicin+Vincristine+Cyclophosphamide+Prednisolone every 14 days||<10||Cunningham |
|Pemetrexed||<10||Hanna N |
|Epirubicin+Oxaliplatin+Capecitabine||<10||Cunningham Sumpter |
|Docetaxel+Cisplatin+Fluorouracil||10-20||Maruyama  Sendur MA  Hacibekiroglu |
Appendix Table 1: FN risks associated with chemotherapy regimens compiled from previous studies.
A total of 274 patients met the inclusion criteria. They consisted mainly of breast and colorectal cancer patients which represents 49% and 29% in respective (Figure 1). Most of the patients were female (66%) and the median age was 52 yrs. Percent of patients received chemotherapy induce high, intermediate or low risk of FN was 10.5%, 22.5%, 67% respectively (Table 1). While, the prescribing of G-CSFs in patients who received chemotherapy inducing intermediate-risk FN without comorbidity and low-risk FN was considered inappropriate (Table 2). Overall, G-CSFs were prescribed appropriately for FN primary prophylaxis in 232 patients and inappropriately in 42 patients which represents 85% and 15% respectively (Figures 2-4). G-CSFs were not prescribed in (97%) 28 out of 29 patients in high risk FN, which considered inappropriate. Additionally, G-CSFs were prescribing appropriately in (81%) 50 out of 62 patients in intermediate-risk. Moreover, G-CSFs were not prescribed in (99%) 181 out of 183 patients in low-risk, which considered appropriate. Twenty-two patients (8%) developed FN among those 17 patients used G-CSF appropriately and for 5 patients G-CSFs was used inappropriately. Only 3 patients who did not receive G-CSFs with chemotherapy induce high-risk developed FN. But interestingly, FN was devolved in 16 out of 22 patients with low-risk chemotherapy and did not receive G-CSFs. The incidence of FN between the appropriate and inappropriate groups did not differ significantly (p=0.315).
|Overall||Appropriate use||Inappropriate use|
|Age (years), median (IQR)||52 (44-60)||52 (43-59)||56 (49-66)|
|F, N (%)||181( 66)||148 (82)||33 (18)|
|M, N (%)||93 (34)||84 (90)||9 (10)|
|Weight (kg), median (IQR)||71 (59-82)||70 (58-82)||77 (66-85)|
|Height (cm), median (IQR)||158 (153-165)||159 (154-166)||157 (153-163)|
|Breast Cancer, N (%)||135 (49)||106 (79)||29 (21)|
|Colorectal Cancer, N (%)||78 (29)||76 (97)||2 (3)|
|Lung Cancer, N (%)||20 (7)||17 (85)||3 (15)|
|Gastric Cancer, N (%)||14 (5)||12 (86)||2 (14)|
|Oesophageal Cancer, N (%)||4 (2)||4 (100)||0 (0)|
|Nasopharyngeal Cancer, N (%)||23 (8)||17 (74)||6 (26)|
|Prophylaxis G-CSFs used, N (%)||6 (2)||1 (17)||5 (83)|
|Total bilirubin ≤ 60 mmol/L, N (%)||274 (100)||232 (85)||42 (15)|
|AST level ≤ 140 U/L, N (%)||274 (100)||232 (85)||42 (15)|
|ALT level ≤ 200 U/L, N (%)||274 (100)||232 (85)||42 (15)|
|CrCl>30 mL/min, N (%)||274 (100)||232 (85)||42 (15)|
|Chemotherapy regimen risk for FN|
|≥ 20%, N (%)||29 (10.5)||1 (3)||28 (97)|
|10-20%, N (%)||62 (22.5)||50 (81)||12 (19)|
|<10%, N (%)||183 (67)||181 (99)||2 (1)|
Table 1: Summary of baseline demographics and patient characteristics.
|Appropriate prescribing||1) Chemotherapy associated with high-risk FN.
2) Chemotherapy associated with intermediate-risk FN with the following criteria (poor renal function, liver dysfunction, advanced age (>65 years), previous chemotherapy with neutropenia, previous radiation therapy with neutropenia, preexisting neutropenia or bone marrow involvement with tumor, previous infection or open wounds, recent surgery, poor performance status, or HIV-infection).
|Inappropriate prescribing||1) Chemotherapy associated with intermediate-risk FN (without the previous criteria).
2) Chemotherapy associated with low-risk FN.
Table 2: Appropriate and inappropriate criteria to evaluate the prescribing pattern of G-CSFs for neutropenia primary prophylaxis.
Previous studies showed that approximately 63%-69% of patients complied with G-CSFs prescribing guidelines for primary prophylaxis [15,16]. At 85%, compliance with the prescribing of G-CSFs for primary prophylaxis is higher at our than at other institutions. Another study found that G-CSFs was being over utilized in patients undergoing chemotherapy associated with low risk of FN and underutilized in patients with high risk of FN. This finding is similar to ours, whereby G-CSFs were underutilized in patients with high risk of FN [17-25]. However, G-CSFs were prescribed appropriately in intermediate-and low-risk patients at our institution. In previous study inappropriate prescribing of G-CSFs increase FN episodes with lung and colorectal cancer on chemotherapy regimens receiving G-CSFs, the probability of high, intermediate and low risk FN was 17%, 18% and 10%, respectively; and 96% of G-CSFs use were not based on guidelines. In our study, the appropriateness of G-CSFs use was not associated with FN incidence in patients received chemotherapy regimens with high risk of FN potential.
Although, the appropriate prescribing is 85% in our institution, developing of hospital guidelines should establish to reduce the impact of inappropriate G-CSFs use. The guidelines should include the risk of FN of each chemotherapy regimen used and whether to prescribe G-CSFs or not. Adding the G-CSFs to the chemotherapy protocol will dramatically decrease inappropriate prescribing. This study is limited by the fact that it was a retrospective study, carried out at a single institution and over a single year. Additionally, some of the chemotherapy FN risks were not reported in the guidelines or in the literature, resulting in the exclusion of five patients. Furthermore, poor documentation made it difficult to determine the inappropriate use of G-CSFs in intermediate-risk cases. Nevertheless, to the best of our knowledge, this is the first report evaluating the use of G-CSFs in Saudi Arabia in general.
At our institution, the prescribing of G-CSFs for FN primary prophylaxis was inappropriate on some occasions. We noticed that the main cause for inappropriate prescribing was lack of G-CSFs prescription with regimens associated with recognized high risk of FN. Pharmacists and clinical pharmacists play major role beside oncology physicians in improving inappropriate prescribing of G-CSFs. Therefore, the development of comprehensive hospital guidelines may reduce the impact of an inappropriate prescribing of G-CSFs. As well as, future studies needed to highlight the FN risk associated with chemotherapy regimens used in practice.
- Lyman GH, Michels SL, Reynolds MW, Barron R, Tomic KS, et al. (2010) Risk of mortality in patients with cancer who experience febrile neutropenia. Cancer 116: 5555-5563.
- Caggiano V, Weiss RV, Rickert TS, Linde-Zwirble WT (2005) Incidence, cost, and mortality of neutropenia hospitalization associated with chemotherapy. Cancer 103: 1916-1924.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. Myeloid Growth Factors.
- Lichthardt S, Kerscher A, Dietz UA, Jurowich C, Kunzmann V, et al. (2016) Original article: role of adjuvant chemotherapy in a perioperative chemotherapy regimen for gastric cancer. BMC Cancer 16: 650.
- Jyoti BS (2015) Accuracy of MRI for Prediction of Response to Neo-Adjuvant Chemotherapy in Triple Negative Breast Cancer Compared to Other Molecular Types. Chemo Open Access 5:175.
- Cooper KL, Madan J, Whyte S, Stevenson MD, Akehurst RL (2011) Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis following chemotherapy: systematic review and meta-analysis. BMC Cancer 11: 404.
- Kuderer NM, Dale DC, Crawford J, Lyman GH (2007) Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: a systematic review. J Clin Oncol 25: 3158-3167.
- Kamioner D, Crawford J, Aapro M (2010) Prophylaxis of chemotherapy-induced febrile neutropenia with granulocyte colony-stimulating factors: where are we now?. Support Care Cancer 18: 529-541.
- Krzemieniecki K, Sevelda P, Erdkamp F, Smakal M, Schwenkglenks M, et al. ( 2014) Neutropenia management and granulocyte colony-stimulating factor use in patients with solid tumours receiving myelotoxic chemotherapy-findings from clinical practice. Support Care Cancer 22: 667-677.
- Bunn PA Jr, Crowley J, Kelly K, Hazuka MB, Beasley K, et al. (1995) Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group. J Clin Oncol 13: 1632-1641.
- Mickelson DM, Hatem SF, Copelan EA (2010) Granulocyte stimulating-colony factor-associated splenic artery rupture. Leuk Lymphoma 51: 335-337.
- Chan KK, Siu E, Krahn MD, Imrie K, Alibhai SM (2012) Cost-utility analysis of primary prophylaxis versus secondary prophylaxis with granulocyte colony-stimulating factor in elderly patients with diffuse aggressive lymphoma receiving curative-intent chemotherapy. J Clin Oncol 30: 1064-1071.
- Strassels SA, Dickson M, Norris LB, Bennett CL (2013) Primary prophylaxis with hematopoietic colony stimulating factor: insights from a Canadian cost-effectiveness analysis. J Natl Cancer Inst 105: 1072-1073.
- Lee S, Knox A, Zeng IS, Coomarasamy C, Blacklock H, et al. (2013) Primary prophylaxis with granulocyte colony-stimulating factor (GCSF) reduces the incidence of febrile neutropenia in patients with non- Hodgkin lymphoma (NHL) receiving CHOP chemotherapy treatment without adversely affecting their quality of life: cost-benefit and quality of life analysis. Support Care Cancer 21: 841-846.
- Butler TW, Waddell JA, Crane BJ, Porter AM (2014) Evaluation of G-CSF use in a single institution and development of pocket reference for primary prophylaxis of chemotherapy-induced febrile neutropenia. J Hematol Oncol Pham 4: 9-14.
- Mousavi S, Dadpoor M, Ashrafi F (2016) Granulocyte colony-stimulating factor use in a large Iranian hospital: comparison with American Society of Clinical Oncology (ASCO) clinical practice guideline. Int J Hematol Oncol Stem Cell Res 10: 85-91.
- Barnes G, Pathak A, Schwartzberg L (2014) G-CSF utilization rate and prescribing patterns in United States: associations between physician and patient factors and GCSF use. Cancer Med 3: 1477-1484.
- Potosky AL, Malin JL, Kim B, Chrischilles EA, Makgoeng SB, et al. (2011) Use of colony-stimulating factors with chemotherapy: opportunities for cost savings and improved outcomes. J Natl Cancer Inst 103: 979-982.
- Nabholtz J, Falkson C, Campos D, Szanto J, Martin M, et al. (2013) Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a randomized, multicenter, phase III trial. J Clin Oncol 21: 968-975.
- Chan A, Chen C, Chiang J, Tan SH, Ng R (2012) Incidence of febrile neutropenia among early-stage breast cancer patients receiving anthracycline-based chemotherapy. Support Care Cancer 20: 1525-1532.
- Kosaka Y, Rai Y, Masuda N, Takano T, Saeki T, et al. (2015) Phase III placebo-controlled, double-blind, randomized trial of pegfilgrastim to reduce the risk of febrile neutropenia in breast cancer patients receiving docetaxel/cyclophosphamide chemotherapy. Support Care Cancer 23: 1137-1143.
- Jenkins P, Freeman S (2009) Pretreatment haematological laboratory values predict for excessive myelosuppression in patients receiving adjuvant FEC chemotherapy for breast cancer. Ann Oncol 20: 34-40.
- Perez EA, Suman VJ, Rowland KM, Ingle JN, Salim M, et al. (2005) Two concurrent phase II trials of paclitaxel/carboplatin/trastuzumab (weekly or every-3-week schedule) as first-line therapy in women with HER2-overexpressing metastatic breast cancer: NCCTG study 983252. Clin Breast Cancer 6: 425-432.
- Gilbar P, McPherson I, Sorour N, Sanmugarajah J (2014) High incidence of febrile neutropenia following adjuvant breast chemotherapy with docetaxel, carboplatin and trastuzumab. Breast Cancer Manage 3: 327-333.
- Valero V, Forbes J, Pegram MD, Pienkowski T, Eiermann W, et al. (2010) Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 Study): two highly active therapeutic regimens. J Clin Oncol 29: 149-156.
- Gligorov J, Doval D, Bines J, Alba E, Cortes P, et al. (2014) Maintenance capecitabine and bevacizumab versus bevacizumab alone after initial first-line bevacizumab and docetaxel for patients with HER2-negative metastatic breast cancer (IMELDA): a randomized, open-label, phase 3 trial. Lancet Oncol 15: 1351-60.
- Diaz-Rubio E, Evans TR, Tabemero J, Cassidy J, Sastre J, et al. (2002) Capecitabine (Xeloda) in combination with oxaliplatin: a phase I, dose-escalation study in patients with advanced or metastatic solid tumors. Ann Oncol 13: 558-565.
- Hacibekiroglu I, Kodaz H, Erdogan B, Turkmen E, Esenkaya A, et al. (2015) Comparative analysis of the efficacy and safety of modified FOLFOX-6 and DCF regimens as first-line treatment in advanced gastric cancer. Mol Clin Oncol 3: 1160-1164.
- Andre T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, et al. (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350: 2343-2351.
- Comella P, Massidda B, Natale D, Putzu C, Sandomenico C, et al. (2011) Efficacy and tolerability of biweekly bevacizumab, irinotecan, folinic acid and fluorouracil intravenous bolus (BIFF Regimen) in patients with metastatic colorectal cancer: the southern Italy cooperative oncology group experience. Clin Colorectal Cancer 10: 42-47.
- Boku N (2009) JCOG trials of systemic chemotherapy for unrespectable or recurrent gastric cancer. Gastric Cancer 12: 43-49.
- Schmiegel W, Reinacher-Schick A, Arnold D, Kubicka S, Freier W, et al. (2013) Capecitabine/irinotecan or capecitabine/oxaliplatin in combination with bevacizumab is effective and safe as first-line therapy for metastatic colorectal cancer: a randomized phase II study of the AIO colorectal study group. Ann Oncol.24: 1580-1587.
- Li W, Xu J, Shen L, Liu T, Guo W, et al. (2014) Phase II study of weekly irinotecan and capecitabine treatment in metastatic colorectal cancer patients. BMC Cancer 14: 986.
- Douillard J, V-303 Study Group (2000) Irinotecan and high-dose fluorouracil/leucovorin for metastatic colorectal cancer. Oncology (Williston Park) 14: 51-55.
- Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, et al. (2008) Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 26: 3543-3551.
- Agelaki S, Bania H, Kouroussis C, Blazoyiannakis G, Souglakos J, et al. (2001) Second-line treatment with vinorelbine and carboplatin in patients with advanced non-small cell lung cancer. A multicenter phase II study. Lung Cancer 34: S77-80.
- LeCaer H, Delhoume JY, Thomas PA, Berard H, Paillotin D, et al. (2005) Multicenter phase II trial of carboplatin/vinorelbine in elderly patients with advanced non-small-cell lung cancer efficacy and impact on quality of life: Group Francais de Pneumo-Cancerologie Study 9902. Clin Lung Cancer 7: 114-120.
- Hanna N, Bunn PA Jr, Langer C, Einhorn L, Guthrie T Jr, et al. (2006) Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol 24: 2038-2043.
- Cunningham D, Hawkes EA, Jack A, , Qian W, Smith P, et al. (2013) Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet 381: 1817-1826.
- Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, et al. (2004) Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol 22: 1589-1597.
- Pereira JR, Cheng R, Orlando M, Kim JH, Barraclough H (2013) Elderly subset analysis of randomized phase III study comparing pemetrexed plus carboplatin with docetaxel plus carboplatin as first-line treatment for patients with locally advanced or metastatic non-small cell lung cancer. Drugs R D 13: 289-296.
- Nasr FL, Chahine GY, Kattan JG, Farhat FS, Mokaddem WT, et al. (2004) Gemcitabine plus carboplatin combination therapy as second-line treatment in patients with relapsed breast cancer. Clin Breast Cancer 5: 117-122.
- Cho EK, Lee WK, Im SA, Lee SN, Park SH, et al. (2005) A phase II study of epirubicin, cisplatin and capecitabine combination chemotherapy in patients with metastatic or advanced gastric cancer. Oncology 68: 333-340.
- Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, et al. (2008) Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 358: 36-46.
- Sumpter K, Harper-Wynne C, Cunningham D, Rao S, Tebbutt N, et al. (2005) Report of two protocol planned interim analyses in a randomized multicenter phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer receiving ECF. Br J Cancer 92: 1976-1983.
- Lin JT, Shih SC, Chang TH, Chang CS (2010) Docetaxel, carboplatin and 5-fluorouracil (TCF) chemotherapy in patients with unresectable metastatic carcinoma of cervix. Gynecol Oncol 117: 65-69.
- Zhao JG, Xiong JP, Xiang XJ, Qiu F, Zhang L, et al. (2009) A phase II trial of epirubicin plus oxaliplatin and fluorouracil as first-line chemotherapy for advanced gastric cancer. Ai Zheng 28: 42-44.
- Ozkan K, Turkkan E, Ender K, Mutlu D, Murat A, et al. (2005) 5-Fluorouracil, epirubicin and cisplatin in the treatment of metastatic gastric carcinoma: a retrospective analysis of 68 patients. Indian J Cancer 42: 85-88.
- Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, et al. (2007) Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med 357: 1705-1715.
- Sendur MA, Ozdemir N, Ozatli T, Yazıci O, Aksoy S, et al. (2014) Comparison the efficacy of second-line modified EOX (epirubicin, oxaliplatin, and capecitabine) and irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) regimens in metastatic gastric cancer patients that progressed on first-line modified docetaxel and cisplatin plus fluorouracil (DCF) regimen. Med Oncol 31: 153.
Citation: Alshehri AF, Alnatsheh A, Aseeri M, Al Fayea T (2017) Evaluation of the Use of Granulocyte Colony-Stimulating Factors (G-CSFs) for Neutropenia Primary Prophylaxis in Solid Tumors at a Tertiary Care Hospital, Retrospective Study. J Pharmacovigil 5: 248. Doi: 10.4172/2329-6887.1000248
Copyright: © 2017 Alshehri AF, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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