Incidence and clinical impact of chemotherapy induced myelotoxicity in cancer patients: An observational retrospective survey

https://doi.org/10.1016/j.critrevonc.2009.03.004Get rights and content

Abstract

Purpose

To evaluate the frequency of chemotherapy-induced myelotoxicity in cancer patients, the related treatment (G-CSF, rHuEPO), and the occurrence of chemotherapy dose reductions, delays or discontinuations.

Patients and methods

We retrospectively collected data from 1175 patients who completed at least four chemotherapy courses at 64 Italian Centres.

Myelotoxicity was defined as anemia (Hb < 10 g/dL) and neutropenia (ANC < 1500/mm3). The study population was divided by age, in 664 adult patients aged ≤65 years and 511 elderly patients, aged >65 years. The association between events during chemotherapy and myelotoxicity indices were assessed by logistic regression.

Results

The median age of the patients was 64 years. Myelotoxicity was observed in 633 patients (53.9%), anemia (<10 g/dL) in 263 (22.4%) and neutropenia in 530 (45.1%); 686 patients (58.5%) showed mild anemia (Hb < 12 g/dL). Dose reductions were observed in 199 patients (16.9%), dose delays in 338 (28.7%), and discontinuations in 157 (13.4%), with no significant difference between age groups.

Myelotoxicity accounted for 20% of treatment withdrawals with no differences between age groups. G-CSF was administered to 53.4% of the neutropenic patients, and rHuEPO to 53.1% of the anemic patients.

Logistic regression analyses showed a significant (P < 0.001) association between chemotherapy dose delays, dose reductions and myelotoxicity. Considering age strata, the association between dose reduction and myelotoxicity was significant. The risk of neutropenia in the adults was higher than in elderly (50.0% vs 38.7%).

Conclusion

Our results show that anemia and neutropenia occur in a substantial proportion of cancer patients receiving chemotherapy, and have an impact on chemotherapy dose delivery. G-CSF and rHuEPO are treatments widely used in about one half of neutropenic and anemic patients.

Particular attention should be given to elderly patients, who are at high risk of myelotoxicity and should be carefully evaluated for the prophylactic use of G-CSF and monitored for the appropriate use of rHuEPO.

Introduction

Anemia and neutropenia are frequent myelotoxic events responsible for chemotherapy delays, discontinuations and dose modifications. As they can impair the efficacy of chemotherapy, a great efforts have being made to minimise the risk of morbidity and mortality [1], [2].

The Functional Assessment of Cancer Therapy-Anaemia (FACT-An) validation study suggested a relationship between hemoglobin (Hb) levels and patients’ quality of life, as the patients with Hb  12 g/dL had a significantly higher mean FACT-An score than those with Hb < 12 g/dL [3].

The European Cancer Anaemia Survey (ECAS) investigated the prevalence, incidence and treatment of anemia in 15,367 cancer patients evaluated for up to six months [4]. The prevalence of anemia was 39.3% at enrolment and 67.0% during the survey, and its incidence was 53.7%. Anemia was treated in 38.9% of the patients (erythropoietic agents 17.4%; transfusions 14.9%; and iron 6.5%), and the mean hemoglobin level for starting treatment was 9.7 g/dL. These results are consistent with the findings of Seshadri et al. [5] concerning 694 Australian patients with a median age of 60 years. Anemia was observed in 57% of the patients and was consistent with tumour type (49% of the patients with lymphoma and myeloma, 85% of those with urogenital cancer). Anemia was treated by transfusions in 36% of the patients, and by iron in 5%; a further 2% were treated with erythropoietic agents. The frequency of anemia treatment varied among tumour types, from 19% (breast cancer) to 60% (leukemia).

Neutropenia is a frequent complication of chemotherapy. Caggiano et al. [6] carried out a retrospective analysis to evaluate the incidence, mortality and hospitalisation associated with neutropenia. There were 20,780 discharges with documentation of cancer chemotherapy and neutropenia. The incidence of hospitalisation due to neutropenia projected to national levels was estimated at 60,294 cases (7.83 cases per 1000 cancer patients), and the mortality rate was estimated at 6.8% (1 death for every 14 hospitalised patients). As expected, neutropenia hospitalisation was particularly common in patients with hematological tumours, with an incidence of 43.3 cases per 1000 patients.

In the last decade, the use of recombinant human erythropoietins (rHuEPO) and granulocyte-colony stimulating factors (G-CSFs) has radically modified the treatment of myelotoxicity due to chemotherapy in clinical practice. The reported response to rHuEPO (defined as an increase in Hb of >2 g/dL) ranges from 32 to 82% [7], and rHuEPO are widely used for cancer-related treatment of anemia in many countries [8], [9], [10], [11]. Recently, concerns about the safety of rHuEPO have been raised and the need to redefine the exact setting for its use has been claimed [12]. However serious risk with the rHuEPO have been observed in clinical setting and hemoglobin ranges not supported by current guidelines [13].

G-CSFs have provided considerable benefits to patients treated with chemotherapy and represent the standard treatment for chemotherapy-induced neutropenia [14], [15], [16], [17], [18], [19].

However, although several guidelines, consensus conferences and authoritative publications are now available for practising physicians, many questions remain open, and the standard approach to the management of cancer-related anemia and neutropenia is far from being defined [20], [21], [22], [23], [24].

On the basis of these previous experiences, CIPOMO (Collegio Italiano Primari Oncologi Medici Ospedalieri) conducted this retrospective observational survey in order to collect information concerning the prevalence and incidence of myelotoxicity, anemia and neutropenia in Italian Community Hospitals, and treatment patterns in cancer patients receiving chemotherapy.

Section snippets

Patients

The study data referred to 1175 patients attending 64 Italian Centres belonging to CIPOMO between July 2005 to January 2006.

The objectives of the study were to evaluate: (i) the frequency of the diagnoses of anemia and neutropenia in patients treated with chemotherapy; (ii) the prescribed treatment for anemia and neutropenia and (iii) the occurrence of chemotherapy dose reductions, delays or discontinuations due to anemia and/or neutropenia.

The eligible patients were >18 year old and had a

Results

Table 1 shows the patients’ characteristics. There were more females in the adult group (73.2% females vs 26.8% males) but no gender difference in the elderly group.

The most frequent cancer site was the breast (390 patients, 33.2%) followed by colon–rectum (299 patients, 25.5%), non-small cell lung cancer (113 patients, 9.6%), ovary (84 patients, 7.1%) and stomach (46 patients, 3.9%). There were more patients with breast cancer in the adult group, and more patients with colon–rectum and NSCLC

Discussion

This retrospective observational survey explored the prevalence and incidence of myelotoxicity, anemia and neutropenia in an Italian population of 1175 cancer patients, treated in Community Hospitals, in accordance with local rules and physician judgment.

In terms of age, the distribution of tumour types and treatments, our population appears to be representative of the general cancer population, as indicated by epidemiological studies [25].

The survey showed that 53.9% of the patients

Conflict of interest

Author has no conflicting interest to declare.

Reviewer

Heidi D. Klepin, M.D., Wake Forest University School of Medicine, Section of Hematology and Oncology, Medical Center Boulevard, Winston-Salem, NC 27157, United States.

Acknowledgments

The authors would like to thank Dr. Simonetta Pignattelli (Medical Affairs, AMGEN, Italy) for supporting the study, Dr. Patrizio Sala, for the statistical analyses, and Dr. Ettore Bichisao for his help in preparing the manuscript. The full list of all the participating CIPOMO Centres is given in Appendix A.

Lazzaro Repetto is Director of Medical Oncology at the Istituto Nazionale Riposo e Cura per Anziani, INRCA—Rome since 2001. After medical degree at the University of Genoa in 1982 he completed his medical training as Fellow of the Department of Hematology University of Genoa, the Department of Medical Oncology Istituto Nazionale per la Ricerca sul Cancro Genoa, and the Department of Medical Oncology at Royal Marsden Hospital, London.

He held the positions of assistant professor and deputy head,

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      Finally, in a retrospective analysis about data of 1175 patients, who completed at least four chemotherapy courses for solid tumors, dose reductions were observed in 17%, dose delays in 29%, and treatment discontinuation in 13%. A significant association between chemotherapy dose delays, dose reductions and myelotoxicity has been established (p < 0.001) (Repetto, 2009). Moreover, such similar results have been found in other large retrospective studies focusing on chemotherapy administration among NHL patients (Picozzi et al., 2001; Lyman et al., 2004).

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    Lazzaro Repetto is Director of Medical Oncology at the Istituto Nazionale Riposo e Cura per Anziani, INRCA—Rome since 2001. After medical degree at the University of Genoa in 1982 he completed his medical training as Fellow of the Department of Hematology University of Genoa, the Department of Medical Oncology Istituto Nazionale per la Ricerca sul Cancro Genoa, and the Department of Medical Oncology at Royal Marsden Hospital, London.

    He held the positions of assistant professor and deputy head, Department of Medical Oncology Istituto Nazionale per la Ricerca sul Cancro Genoa.

    He is member of several scientific societies and author of 180 papers.

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