Lipegfilgrastim for prophylaxis of chemotherapy-induced neutropenia in Dutch patients.

BACKGROUND: Chemotherapy (CT)-induced neutropenia and febrile neutropenia (FN) can lead to changes in the treatment plan, potentially worsening the cancer outcome. This study evaluated the effect of the glycopegylated granulocyte-colony stimulating factor lipegfilgrastim, used as primary (PP) or secondary prophylaxis (SP), on treatment modifications in adult patients receiving cytotoxic CT with or without biological/targeted therapy (BT) for solid and haematological tumours. METHODS: This phase 4, prospective, observational study was conducted in eight centres in the Netherlands, in 2015-2017. Other study objectives were to characterise the population of cancer patients receiving lipegfilgrastim, to evaluate the incidence of CT-induced neutropenic events, and to assess safety. RESULTS: Of 142 patients, 73.94% had breast cancer and 55.63% received CT in the adjuvant setting. Most patients received lipegfilgrastim as PP (74.65%) and were at low (34.51%) or high risk (39.44%) of FN. CT dose delays were recorded for 22.64% and 36.11% of patients receiving lipegfilgrastim for PP and SP, respectively. CT dose reductions were recorded for 2.11% of patients; no CT dose omissions and one BT dose omission occurred. FN and grade III/IV neutropenia were reported for 5.63% and 9.86% of patients, respectively; associated hospitalisations were rare. The most frequently lipegfilgrastimrelated adverse events (AE) were myalgia, bone pain, and back pain. Serious AEs (55) were reported for 30 (21.13%) patients. There were two deaths, unrelated to lipegfilgrastim administration. CONCLUSION: Administration of lipegfilgrastim in routine clinical practice in the Netherlands results in limited CT/BT dose modifications and low incidence of neutropenic events, with no new safety concerns.

Long-term results of a randomised phase III trial of weekly versus three-weekly paclitaxel/platinum induction therapy followed by standard or extended three-weekly paclitaxel/platinum in European patients with advanced epithelial ovarian cancer.

BACKGROUND: Weekly paclitaxel/carboplatin might improve survival in platinum-resistant epithelial ovarian cancer (EOC). We compared efficacy of first-line weekly to three-weekly paclitaxel/cis- or carboplatin (PCw and PC3w) induction therapy, followed by either three or six PC3w cycles. PATIENTS AND METHODS: In this multicentre, randomised phase III trial with 2×2 design, patients with FIGO stage IIb-IV EOC were randomised to six cycles PCw (paclitaxel 90mg/m(2), cisplatin 70mg/m(2) or carboplatin AUC 4) or three cycles PC3w (paclitaxel 175mg/m(2), cisplatin 75mg/m(2) or carboplatin AUC 6), followed by either three or six cycles PC3w. Primary endpoints were progression free survival (PFS) and overall survival (OS). Secondary endpoints were response rate (RR) and toxicity. RESULTS: Of 267 eligible patients, 133 received PCw and 134 PC3w. The first 105 patients received cisplatin, after protocol amendment the subsequent 162 patients received carboplatin. Weekly cisplatin was less well tolerated than weekly carboplatin. All PC3w cycles were well tolerated. At the end of all treatments, RR was 90.8% with no differences between the treatment arms. After a follow-up of median 10.3years (range 7.1-14.8), median PFS was 18.5 (95% confidence interval (CI) 15.9-21.0) months for PCw and 16.4 (95% CI 13.5-19.2) months for PC3w (p=0.78). Median OS was 44.8 (95% CI 33.1-56.5) months for PCw and 41.1 (95% CI 34.4-47.7) months for PC3w (p=0.98). CONCLUSIONS: There was no benefit in terms of OS, PFS or RR for a weekly regimen nor for extended chemotherapy as first-line treatment for EOC in European patients.

Prevention of anaemia by early intervention with once weekly epoetin alfa during chemotherapy.

This study compared the effects of early intervention with standard use of epoetin alfa on haemoglobin (Hb) levels and transfusion requirements in cancer patients receiving chemotherapy. Patients with Hb>10 and < or= 12 g/dL were randomised 1:1 to epoetin alfa (40,000 IU, subcutaneously, once weekly), initiated within 7d of the start of the first on-study chemotherapy cycle (defined as early intervention) versus epoetin alfa when Hb

Weekly paclitaxel as first-line chemotherapy for elderly patients with metastatic breast cancer. A multicentre phase II trial.

Paclitaxel is a cytotoxic agent with proven antitumour activity in metastatic breast cancer. Weekly administration of paclitaxel has demonstrated sustained efficacy together with a more favourable toxicity profile (e.g. less myelotoxicity) than the 3-weekly administration. This study evaluates the activity and toxicity of weekly paclitaxel (Taxol(R)) as first-line chemotherapy in elderly patients (>70 years of age) with hormone-refractory metastatic breast cancer. Patients with metastatic breast cancer received 80 mg/m(2) paclitaxel administered weekly on days 1, 8 and 15 of a 28-day cycle. Additional cycles were given until disease progression, or unacceptable toxicity. A dose increase to 90 mg/m(2) was allowed in the absence of toxicity. 26 Patients received a total of 101 cycles (median 4, range 1-11). 22 patients completed at least two cycles (six administrations). In 23 patients who were evaluable for response, there were 10 partial responses (38%), 9 patients with stable disease (35%), while 4 patients had disease progression (15%). The median duration of response was 194 days (>6 months). Overall treatment was relatively well tolerated, but 8 patients (32%) had to prematurely discontinue treatment because of fatigue. Neuropathy >grade 1 was noted only after five or more cycles in 4 patients. Weekly paclitaxel at this dose and schedule is an effective treatment regimen in the elderly patient with metastatic breast cancer, and is feasible, but yields relevant fatigue in a subset of patients.