Continuous infusion or subcutaneous injection of granulocyte-macrophage colony-stimulating factor: increased efficacy and reduced toxicity when given subcutaneously

Honkoop, Aafke H.; Hoekman, K.; Wagstaff, John; Groeningen, C.J. van; Vermorken, Jan B.; Boven, Epie; Pinedo, H.M.

doi:10.1038/bjc.1996.502

Cited by 14 publications

(3 citation statements)

References 30 publications

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“…GM-CSF 250 µg/m 2 /day was administered from days 2-11, in the first four patients as a continuous i.v. infusion and in the following 38 patients s.c. [17]. Initially, some patients received fewer than six cycles.…”

Section: Treatmentmentioning

confidence: 99%

Prolonged Neoadjuvant Chemotherapy with GM-CSF in Locally Advanced Breast Cancer

Honkoop

Bakker²,

Hoekman³

et al. 1999

The Oncologist

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Background. Neoadjuvant chemotherapy improves survival in patients with locally advanced breast cancer (LABC). Usually three to four cycles of conventional‐dose neoadjuvant chemotherapy are administered prior to local therapy, and another three cycles thereafter. In an attempt to improve results, we increased the dosages and applied GM‐CSF, which, besides being a hematopoietic growth factor, has become increasingly known for its immunostimulatory effects, which might enhance the antitumor effect. Methods. Forty‐two patients with stage IIIA or IIIB breast cancer were treated with doxorubicin (A) (90 mg/m2) and cyclophosphamide (C) (1,000 mg/m2) at three‐weekly intervals. In the second and fourth cycle a 10% dose reduction of both agents was applied. On the second day GM‐CSF 250 μg/m2/day was started and given for 10 days. Initially, some patients were treated with ≤ four cycles, but as the study progressed and toxicity appeared tolerable, six cycles were given whenever possible. After the chemotherapy, patients underwent surgery and postoperative radiotherapy. Results. The response rate for the whole group to AC was 98% (95% confidence interval 94%‐100%), with a clinical complete response rate of 50% (95% confidence interval 35%‐65%). Six patients had a pathological complete response. Median follow‐up from the start of chemotherapy is 49 months (range 10‐100). The disease‐free survival (DFS) at three years is 57% and the overall survival (OS) at three years is 79%. There is a significant trend for improved DFS (p = 0.0000) and OS (p = 0.0002) with increasing number of cycles. Conclusion. The results of the present study with neoadjuvant dose‐intensive AC chemotherapy and GM‐CSF compare favorably with previous studies in patients with LABC. This is most apparent in patients who received six cycles of neoadjuvant chemotherapy. We hypothesize that these encouraging results are probably related to the prolonged presence of the primary tumor, and to the long‐term administration of GM‐CSF with the primary tumor and axillary lymph nodes in situ. Therefore, a randomized study is warranted. We already initiated an international randomized trial in patients with LABC in order to answer two questions. First, does prolonged neoadjuvant chemotherapy result in an improved DFS and OS in comparison with the conventional approach, and secondly, what is the effect of GM‐CSF in this approach in comparison with G‐CSF?

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Section: Treatmentmentioning

confidence: 99%

Prolonged Neoadjuvant Chemotherapy with GM-CSF in Locally Advanced Breast Cancer

Honkoop

Bakker²,

Hoekman³

et al. 1999

The Oncologist

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“…Although package inserts for CSFs consider intravenous and subcutaneous administration to be equipotent, adult data have found that 2-4 times dosing is required to achieve equivalent effect when either G-CSF or GM-CSF is given intravenous as compared to subcutaneous (Eguchi et al 1990 ;Kaneko et al 1991 ;Stute et al 1995 ;Honkoop et al 1996 ). Adult guidelines all suggest subcutaneous administration for CSFs ESMO 2007 ;Aapro et al 2011 ).…”

Section: Route Of Administrationmentioning

confidence: 99%

Supportive Care in Pediatric Oncology

Feusner¹,

Hastings²,

Agrawal³

2015

Pediatric Oncology

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Each volume of the series "Pediatric Oncology" covers the whole spectrum of the disease concerned, from research issues to clinical management, and is edited by internationally highly respected experts in a comprehensive and clearly structured way. The user-friendly layout allows quick reference to in-depth information. The series is designed for all health-care personnel interested in high-level education in pediatric oncology.

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“…Toxicity may also be schedule-dependent, as continuous intravenous infusion of sargramostim causes more adverse effects than subcutaneous injection. [89] There has been some concern that GM-CSF may contribute to lower platelet counts, [27,28,90] possibly by causing stimulation of platelet-consuming Kupffer cells in the liver. [91] However, because other randomised paediatric studies [26,92] have reported increased platelet counts and the need for fewer platelet transfusions when GM-CSF is used as primary prophylaxis, firm conclusions are difficult to reach.…”

Section: Toxicity Spectrum Of G-csf and Gm-csfmentioning

confidence: 99%

Haemopoietic Growth Factors in Paediatric Oncology

Wagner

Furman

2001

Paediatric Drugs

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Recombinant haemopoietic growth factors (HGFs) are an attractive adjunct to reduce morbidity from chemotherapy regimens and their use has become widespread in paediatric oncology. Although patients receiving HGFs often have faster haematological recovery after intensive chemotherapy, this does not always translate into meaningful clinical benefits. This article reviews the clinical effectiveness of HGFs in a variety of different contexts. Most published studies have used granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) as prophylaxis to ameliorate the subsequent neutropenia following intensive chemotherapy. These 2 agents have also been used to mobilise peripheral blood stem cells for autologous transplantation. HGFs specific for anaemia and thrombocytopenia are currently in paediatric clinical trials and it is hoped that the proper context and administration strategy can be found to make their use clinically effective. This article also reviews data on toxicity, specifically focusing on differences between various formulations of growth factors. HGFs are expensive, and cost-benefit analyses reviewed in this article give an important perspective on the financial aspects of paediatric cancer care. Because HGFs do not benefit every child receiving chemotherapy and overuse increases costs and may result in unnecessary adverse effects, evidence-based guidelines for their rational use in paediatric oncology are proposed.

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Continuous infusion or subcutaneous injection of granulocyte-macrophage colony-stimulating factor: increased efficacy and reduced toxicity when given subcutaneously

Cited by 14 publications

References 30 publications

Prolonged Neoadjuvant Chemotherapy with GM-CSF in Locally Advanced Breast Cancer

Prolonged Neoadjuvant Chemotherapy with GM-CSF in Locally Advanced Breast Cancer

Supportive Care in Pediatric Oncology

Haemopoietic Growth Factors in Paediatric Oncology

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