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ORIGINAL ARTICLE: SUPPORTIVE CARE AND OTHERS
Year : 2020  |  Volume : 9  |  Issue : 1  |  Page : 59-61

Role of Cresp® in the management of chemotherapy-induced anemia in cancer patients: A real-world clinical practice audit


1 Department of Medical Oncology, Sum Hospital, Bhubaneswar, Odisha, India
2 Department of Medical Oncology, RCC, Patna, Bihar, India
3 Department of Medical Oncology, Yashoda Hospital, Secunderabad, Telangana, India
4 Department of Medical Oncology, Asian Cancer Institute, Mumbai, Maharashtra, India
5 Department of Medical Oncology, Kerala Institute of Medical Sciences, Trivandrum, Kerala, India
6 Department of Medical Oncology, Apollo Specialty Hospital, Chennai, Tamil Nadu, India
7 Department of Medical Oncology, Mohandai Oswal Hospital, Ludhiana, Punjab, India
8 Department of Medical Oncology, BLK Superspeciality Hospital, Delhi, NCR, India
9 Department of Medical Oncology, Naik Hospital, Baroda, Gujarat, India
10 Department of Medical Oncology, Mumbai Oncocare Center, Mumbai, Maharashtra, India
11 Department of Medical Oncology, Apollo Hospital, Kolkata, West Bengal, India
12 Department of Pain and Palliative Care, Saroj Gupta Cancer Hospital, Kolkata, West Bengal, India
13 Department of Medical Oncology, Batra Cancer Center, Delhi, NCR, India
14 Department of Medical Oncology, Fortis Hospital, Mumbai, Maharashtra, India
15 Department of Medical Oncology, Omega Hospital, Hyderabad, Telangana, India
16 Department of Medical Oncology, Deenanath Mangeshkar Hospital, Pune, Maharashtra, India
17 Department of Medical Oncology, Shalby Cancer and Research Institute, Ahmedabad, Gujarat, India

Date of Web Publication26-Dec-2019

Correspondence Address:
Prof. Purvish M Parikh
Department of Medical Oncology, Shalby Cancer and Research Institute, Ahmedabad, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sajc.sajc_246_19

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  Abstract 

Introduction: Anemia is a common, underestimated problem in cancer patients receiving myelosuppressive chemotherapy and has significant adverse effect on the quality of life and outcome. Darbepoetin has been shown to be effective in this setting, but controversy surrounds it actual use. Methods: We analyzed prospectively collected clinical practice data of patients receiving darbepoetin in a real-world setting for this retrospective audit. Patients with baseline hemoglobin (Hb) of <11 g/dl were included in this analysis. Their medical records were audited using a predetermined 35-point pro forma. Results: There were a total of 274 patients with advanced cancer receiving myelosuppressive chemotherapy who had baseline Hb <11 g/dl and who were given darbepoetin. Head-and-neck squamous cell carcinoma, lung cancer, and breast cancer were the most common cancers. Their median baseline Hb was 8.9 g/dl which rose to 11.2 g/dl at the end of commenced therapy, along with improved symptomatology. There were no new toxicities, and only two patients required discontinuation of darbepoetin due to toxicity. Conclusion: Darbepoetin is safe and effective in the prevention and management of anemia among patients receiving myelosuppressive chemotherapy.

Keywords: Hemoglobin, India, prophylaxis, quality of life, supportive care


How to cite this article:
Biswas G, Pandey A, Ghadyalpatil N, Lokeshwar N, Thomas B, Ramesh A, Arora Y, Dodagoudar C, Naik V, Joshi A, Ghosh I, Roy R, Kunjahari M, Singh T, Satya PD, Hingmire S, Parikh PM. Role of Cresp® in the management of chemotherapy-induced anemia in cancer patients: A real-world clinical practice audit. South Asian J Cancer 2020;9:59-61

How to cite this URL:
Biswas G, Pandey A, Ghadyalpatil N, Lokeshwar N, Thomas B, Ramesh A, Arora Y, Dodagoudar C, Naik V, Joshi A, Ghosh I, Roy R, Kunjahari M, Singh T, Satya PD, Hingmire S, Parikh PM. Role of Cresp® in the management of chemotherapy-induced anemia in cancer patients: A real-world clinical practice audit. South Asian J Cancer [serial online] 2020 [cited 2020 Jul 5];9:59-61. Available from: http://journal.sajc.org/text.asp?2020/9/1/59/274058


  Introduction Top


The European Cancer Anaemia Survey study involving 24 countries reported that 83% of cancer patients receiving chemotherapy develop anemia during their course of illness.[1],[2] Such patients with anemia also have fatigue, weakness, breathlessness, poor performance status, and worse quality of life (QoL).[3],[4] Anemia in cancer patients has also been associated with higher mortality and poorer prognosis.[5] One important factor is due to underreporting of chemotherapy-induced anemia (CIA) – with more than half of them not receiving anemia directed therapy during treatment of their cancer.

Alkylating agents and platinum-based chemotherapy have double the risk of anemia.[1],[6] Low baseline hemoglobin (Hb)(≤12.9 g/dL in females and ≤13.4 dL in males) and concurrent treatment with chemotherapy/radiation therapy are also risk factors of CIA.[1] Patients with lung cancer or gynecologic cancer also have higher risk for anemia, being 39% for single-modality treatment (either chemotherapy or radiation therapy) and 50% for concomitant chemoradiotherapy (50%).[3]

Among cancer patients receiving chemotherapy and developing anemia (Hb ≤11 g/dL), 63% are shown to document moderate-to-severe fatigue.[7] Other features commonly seen in CIA, such as insomnia, anorexia, depression peripheral edema, sustained tachycardia, chest pain, and exertional dyspnea, also impair QoL substantially.[7],[8],[9] Fortunately, these symptoms have been shown to improve along with rise in Hb levels.[10]

While the treatment options for CIA include erythropoiesis-stimulating agents (ESAs), iron supplementation, or transfusion, our focus in this study is to document the use of darbepoetin biosimilar (Cresp®) in a real-world clinical practice setting.[11],[12],[13],[14]


  Methods Top


This is an audit of prospectively documented data of patients with advanced cancer receiving chemotherapy and whose baseline Hb was <11 g/dl. Those who also received darbepoetin in a real-world setting (2.25 μg/kg/week given three weekly) were included in this analysis.[15],[16] Their medical records were scrutinized till the end of chemotherapy and 35 parameters were analyzed. Status of cancer [Table 1] at baseline and last follow-up (FU), adherence to chemotherapy and Cresp scheduling, predetermined clinical features, Hb level, and requirement of red blood cell (RBC) transfusions [Table 2], as well as toxicities [Table 3], were the focus of this evaluation.
Table 1: Site of primary tumor (type of cancer)

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Table 2: Clinical features at baseline and end of chemotherapy

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Table 3: Side effects during darbepoetin (Cresp®) therapy

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  Results Top


Data from 274 patients (159 males and 115 females) fulfilled the requirement for audit. The median age of these patients was 47 years (range: 21–86 years).

All patients were in advanced stage of the disease (Stage III or IV), requiring potentially myelosuppressive chemotherapy as part of their standard of care treatment.

All patients received potentially myelosuppressive combination chemotherapy (two- or three-drug combination protocols) for six to eight cycles. Nearly 39% of patients received platinum-based combination chemotherapy. Drugs used included gemcitabine, pemetrexed, 5-fluorouracil, docetaxel, paclitaxel, oxaliplatin, capecitabine, adriamycin, carboplatin, cisplatin, And darbepoetin (Cresp, Dr. Reddy's Laboratories, Hyderabad, Telengana, India) which were administered 500 μg subcutaneously for every three weeks.

Of the 274 patients who commenced therapy (CT), 233 were able to complete the intended CT (29 had Progressive Disease (PD), 5 due to toxicity, and 7 either died or were lost to FU). Of the 233 patients who were evaluated at the end of CT, 61 (26.18%) achieved complete response, 107 (45.92%) partial response, and 65 (27.90%) stable disease.

Three-weekly Cresp doses were given for a median of four times (range: 1–8 times). The major reason for missing or discontinuing Cresp was due to patient's wish (financial reasons). Cresp was discontinued due to toxicity only in two cases. The median baseline Hb was 8.9 g/dl (range: 6–10 g/dl). The last documented Hb was a median of 11.2 g/dl (range: 9.41–14.6 g/dl). Eight patients required RBC transfusion and were considered as failure of Cresp.


  Discussion Top


Erythropoietin (EPO) is produced endogenously in humans and is responsible for regulating maturation, proliferation, and differentiation of RBCs.[17] Chemotherapy myelosuppression reduces the endogenous production of EPO, leading to anemia. Thus, the use of pharmacological doses of ESA treatments is aimed at overcoming the effect of chemotherapy-induced myelosuppression in the EPO-deficient setting.

Cancer patients on chemotherapy need support when their Hb concentration falls below 10 g/dL.[18] Darbepoetin alfa (as compared to conventional EPO) needs to be administered less frequently – having a longer half-life with improved biologic activity.[12],[15] Close monitoring of patients receiving darbepoetin is mandatory for efficacy, toxicity, and dose modification as per guidelines, and the US Food and Drug Administration even issued a black box warning.[19] However, the experience on either side of the Atlantic ocean has been a lesson in contrast. While the USA floundered and faced significant toxicity, Europe was able to continue using EPO without safety issues. The fundamental difference was in the adherence to the guidelines in Europe – with careful attention to all recommendations – in which patients should consider EPO, Hb level at which to start EPO, dose of EPO to be given, frequency of monitoring, criteria for dose adjustments, as well as level of Hb at which to discontinue further EPO.

These are the largest data on the use of Cresp (darbepoetin biosimilar) in cancer patients. They reflect its use in a multitude of common solid tumors including head-and-neck, lung, and breast cancers. Administration of long-acting Cresp allowed seamless integration into the patients' chemotherapy schedule, without increasing the need to visit health-care professionals/hospitals. The median increase in the Hb level from baseline was 2.3 g/dl, indicating a very good response. Eight patients required RBC transfusions and two other patients required discontinuation of Cresp due to toxicity. This gives an overall failure rate of only 4.29% (10/233).[20],[21],[22] Anemia-related symptoms also showed improvement in the majority of patients. Toxicity was in line with published literature, and there were no unexpected or new safety concerns.

Initial fear that darbepoetin is associated with higher (22%) cardiovascular and/or thromboembolic adverse events as compared to placebo (15%) has not been proven to be appropriate in subsequent randomized controlled trials.[23] Hence, the fear of adverse impact on overall survival has also been shown to be incorrect by several recent publications.[24],[25],[26],[27],[28]

Thus, the correct use of ESAs to treat anemia in cancer patients receiving myelosuppressive chemotherapy is appropriate, safe, and beneficial.[29] In order to maximize the benefit for patients, it is recommended to follow published guidelines in general.[30],[31] For individual patients, management may also be necessary to personalize information on energy conservation methods, diet modification, and graded exercise scheduling – aspects entirely under the control of the patient/family, and following related doctors instructions are vital to optimise treatment benefit. Doing so has also been shown to provide cost-effective management of patients.[32]

In summary, the take-home messages are shown in [Table 4].
Table 4: Take-home messages

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  Conclusion Top


Darbepoietin is safe and effective in the prevention and management of anemia among patients receiveing myselosuppressive chemotherapy. Cresp should be considered in all solid tumor patients with high risk of chemotherapy induced anemia as well as those who develop the anemia while on chemotherapy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Barrett-Lee PJ, Ludwig H, Birgegård G, Bokemeyer C, Gascón P, Kosmidis PA, et al. Independent risk factors for anemia in cancer patients receiving chemotherapy: Results from the European Cancer Anaemia Survey. Oncology 2006;70:34-48.  Back to cited text no. 1
    
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Steinmetz T, Schröder J, Plath M, Link H, Vogt M, Frank M, et al. Antianemic treatment of cancer patients in German routine practice: Data from a prospective cohort study-the tumor anemia registry. Anemia 2016;2016:8057650.  Back to cited text no. 14
    
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Charu V, Saidman B, Ben-Jacob A, Justice GR, Maniam AS, Tomita D, et al. A randomized, open-label, multicenter trial of immediate versus delayed intervention with darbepoetin alfa for chemotherapy-induced anemia. Oncologist 2007;12:1253-63.  Back to cited text no. 18
    
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Rizzo JD, Brouwers M, Hurley P, Seidenfeld J, Arcasoy MO, Spivak JL, et al. American Society of Clinical Oncology/American Society of Hematology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer. J Clin Oncol 2010;28:4996-5010.  Back to cited text no. 19
    
20.
Smith SW, Sato M, Gore SD, Baer MR, Ke X, McNally D, et al. Erythropoiesis-stimulating agents are not associated with increased risk of thrombosis in patients with myelodysplastic syndromes. Haematologica 2012;97:15-20.  Back to cited text no. 20
    
21.
Harnan S, Ren S, Gomersall T, Everson-Hock ES, Sutton A, Dhanasiri S, et al. Association between transfusion status and overall survival in patients with myelodysplastic syndromes: A systematic literature review and meta-analysis. Acta Haematol 2016;136:23-42.  Back to cited text no. 21
    
22.
Revicki DA, Stull D, Vernon M, Rader M, Tomita D, Viswanathan HN, et al. Assessing the effect of darbepoetin alfa on patient-reported fatigue in chemotherapy-induced anemia in four randomized, placebo-controlled clinical trials. Qual Life Res 2012;21:311-21.  Back to cited text no. 22
    
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Gordon D, Nichols G, Ben-Jacob A, Tomita D, Lillie T, Miller C, et al. Treating anemia of cancer with every-4-week darbepoetin alfa: Final efficacy and safety results from a phase II, randomized, double-blind, placebo-controlled study. Oncologist 2008;13:715-24.  Back to cited text no. 23
    
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Zachariah M, Elshinawy M, Alrawas A, Bashir W, Elbeshlawi I, Tony S, et al. Single dose darbepoetin alfa is useful in reducing red cell transfusions in leukemic children receiving chemotherapy. Pediatr Hematol Oncol 2014;31:442-7.  Back to cited text no. 24
    
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Ohashi Y, Uemura Y, Fujisaka Y, Sugiyama T, Ohmatsu H, Katsumata N, et al. Meta-analysis of epoetin beta and darbepoetin alfa treatment for chemotherapy-induced anemia and mortality: Individual patient data from Japanese randomized, placebo-controlled trials. Cancer Sci 2013;104:481-5.  Back to cited text no. 28
    
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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