Plinabulin and Pegfilgrastim in Combination for the Prevention of Chemotherapy-Induced Neutropenia in Patients with Breast Cancer (PROTECTIVE-2): A Randomized Trial

PurposePlinabulin is a non-granulocyte colony-stimulating factor (G-CSF) novel small molecule with both anticancer and myeloprotective effects. Single-agent plinabulin is myeloprotective in the first week of the chemotherapy cycle, and pegfilgrastim in the second week. We assessed the efficacy and safety of the combination of plinabulin and pegfilgrastim for the prevention of chemotherapy-induced neutropenia (CIN) following chemotherapy.MethodsThis randomized, open-label, Phase 2 trial enrolled patients with breast cancer. All received docetaxel 75 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 on Day 1. In the combined therapy cohort, patients received plinabulin 20 mg/m2 on Day 1 and 1.5, 3, or 6 mg pegfilgrastim on Day 2. The primary objective was to establish the recommended Phase 3 dose (RP3D). Secondary endpoints included absolute neutrophil count (ANC) nadir, relative dose intensity (RDI), and incidence of adverse events including neutropenia and bone pain.ResultsIn total, 115 patients were randomized and evaluated. The combination therapy at the RP3D (plinabulin 20 mg/m2 and pegfilgrastim 6 mg) was well-tolerated and had superior CIN prevention in terms of Grade 4 and Grade 3/4 neutropenia frequency, absolute neutrophil count (ANC) nadir, higher relative dose intensity (RDI), less bone pain, and less toxicity burden when compared with pegfilgrastim 6 mg alone.ConclusionPlinabulin combined with pegfilgrastim at the RP3D (plinabulin 20 mg/m2 Day 1 and pegfilgrastim 6 mg Day 2) had more favorable efficacy, safety, and tolerability profiles and lower bone pain incidence than did pegfilgrastim alone.Trial information Clinical Trial Registration: ClinicalTrials.gov NCT04227990Date registered: January 14, 2020 Retrospectively registered

Efficacy and Safety of Lipegfilgrastim for the Prophylaxis of Chemotherapy-induced Neutropenia in Breast Cancer Patients in Poland

IntroductionLipegfilgrastim is a long-acting glycopegylated granulocyte-colony stimulating factor (G-CSF) used to prevent chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN). The aim of the current study was to obtain data on the drug efficacy and safety in real-world clinical practice.Material and methodsThis is an exploratory analysis of Polish breast cancer patients participating in a pan-European study of lipegfilgrastim in primary and secondary prophylaxis for patients receiving cytotoxic chemotherapy (Lonquex ObsErvational Cohort Study, LEOS). Patients were followed since the start of neutropenia prophylaxis until 6 to 8 weeks after the last dose of the lipegfilgrastim . The efficacy measures were chemotherapy dose reductions, omissions, delays and the proportion of the planned cumulative dose actually delivered.ResultsA total of 45 mostly high risk of FN patients were included in the analysis. Overall, 31 of 212 chemotherapy cycles (14.6%) were delayed in 19 patients (42.2%). Cumulative dose of chemotherapy was reduced in 1.4% of the cycles in 4.4% of the patients. The mean percentage of cumulative dose planned actually administrated was 99.95% across all cycles. Only one patient had FN. There were 15 episodes of neutropenia in 3 patients (6.7%), A total of 69 adverse events were reported, which 65% were drug-related. The most common were musculoskeletal pain (17.8%) and myalgia (11.1%) Four adverse events were serious and two of them were related to lipegfilgrastim.ConclusionsLipegfilgrastim proved to be effective and well-tolerated for CIN prophylaxis in patients with breast cancer receiving myelosuppressive chemotherapy in a real-life setting.

Not all hematopoietic growth factors are created equal: should we gain information for their use with immunotherapy?

Myeloid growth factors, either granulocyte colony-stimulating factor (CSF) or granulocyte-macrophage CSF, are widely used to reduce the incidence and severity of chemotherapy-induced neutropenia by prophylactic or therapeutic administration. However, their activity in the novel therapeutic regimens, which often rely on the association between immunotherapy and chemotherapy, has not been thoroughly characterized yet. This paper presents some of the preclinical and clinical research regarding the putative interplay between myeloid growth factors and the immune system, advocating further studies to elucidate their potential positive or negative consequences on the outcomes when administered with immunotherapeutic agents.

Effect of chamomile on chemotherapy-induced neutropenia: a pilot open-label controlled trial

Neutropenia is a common complication of chemotherapy in leukemic patients. An herbal formulation of chamomile was hypothesized to be effective on neutropenia. A group of healthy volunteers and two groups of patients received chamomile oral drop to be compared with a control group of neutropenic patients. Results showed an increase of white blood cells and resolution of neutropenia in all groups except for the control group. In conclusion, chamomile could be used as an effective complementary medicine for increasing the immunity of neutropenic patients (in addition to healthy individuals). Keywords: Chamomile; Leukemia; Chemotherapy; Neutropenia; Integrative Medicine; Persian Medicine

Same-day versus next-day pegfilgrastim or pegfilgrastim-cbqv in patients with lymphoma receiving CHOP-like chemotherapy

Aim: To compare the incidence of febrile neutropenia and related outcomes of prophylactic same-day versus next-day pegfilgrastim/pegfilgrastim-cbqv in patients with lymphoma receiving cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone (CHOP)-like chemotherapy. Methods: Retrospective, real-world, single-institution study. Results: 93 patients received 460 cycles of CHOP-like chemotherapy. The incidence of febrile neutropenia and grade 3/4 chemotherapy-induced neutropenia was 5 and 16.5%, respectively. In 401 cycles pegfilgrastim was administered same-day versus 12 cycles next-day. Febrile neutropenia occurred in 17 cycles versus 0 cycles (p = 1.00) and grade 3/4 chemotherapy-induced neutropenia in 65 cycles (16.2%) versus 1 cycle (16.7%; p = 1.00) with same-day versus next-day pegfilgrastim administration, respectively. Conclusion: Pegfilgrastim may be safely administered on the same day as chemotherapy in patients with lymphoma receiving CHOP-like chemotherapy.