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H Piersma

Publications and source records attributed to H Piersma.

8 recordsLinked to original sources
PubMed2002

Reduced 5-FU clearance in a patient with low DPD activity due to heterozygosity for a mutant allele of the DPYD gene.

5-fluorouracil pharmacokinetics, dihydropyrimidine dehydrogenase-activity and DNA sequence analysis were compared between a patient with extreme 5-fluorouracil induced toxicity and six control patients with normal 5-fluorouracil related symptoms. Patients were treated for colorectal cancer and received chemotherapy consisting of leucovorin 20 mg m(-2) plus 5-fluorouracil 425 mg m(-2). Blood sampling was carried out on day 1 of the first cycle. The 5-fluorouracil area under the curve(0-->3h) in the index patient was 24.1 mg h l(-1) compared to 9.8+/-3.6 (range 5.4-15.3) mg h l(-1) in control patients. The 5-fluorouracil clearance was 520 ml min(-1) vs 1293+/-302 (range 980-1780) ml min(-1) in controls. The activity of dihydropyrimidine dehydrogenase in mononuclear cells was lower in the index patient (5.5 nmol mg h(-1)) compared to the six controls (10.3+/-1.6, range 8.0-11.7 nmol mg h(-1)). Sequence analysis of the dihydropyrimidine dehydrogenase gene revealed that the index patient was heterozygous for a IVS14+1G>A point mutation. Our results indicate that the inactivation of one dihydropyrimidine dehydrogenase allele can result in a strong reduction in 5-fluorouracil clearance, causing severe 5-fluorouracil induced toxicity.

Aged↗
PubMed2000

Feasibility of a dose-intensive CMF regimen with granulocyte colony-stimulating factor as adjuvant therapy in premenopausal patients with node-positive breast cancer.

Our aim was to study the feasibility of an intensified intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) schedule with the aim to escalate dose intensity (DI). Twenty-three premenopausal breast cancer patients received 6 cycles of adjuvant CMF intravenously on days 1 and 8 every 3 weeks and granulocyte colony-stimulating factor days 9-18. Endpoints were DI and toxicity. Twenty-one out of 23 patients (91%) received the projected total dose and reached > or =85% of the projected DI. Compared to 'classical' CMF, all patients reached > or = 111% DI. Nine patients received the planned schedule without delay. Thirteen patients (57%) were treated for infection and four patients (17%) were hospitalized for febrile neutropenia. Twelve patients received red blood cell transfusions (52%). Radiation therapy (n = 6) had no adverse impact on dose intensity or haematological toxicity. This dose-intensified CMF schedule was accompanied by enhanced haematological toxicity with clinical sequelae, namely fever, intravenous antibiotics and red blood cell transfusions, but allows a high dose intensity in a majority of patients.

Adult↗
PubMed1997

Paclitaxel, ifosfamide and cisplatin with granulocyte colony-stimulating factor or recombinant human interleukin 3 and granulocyte colony-stimulating factor in ovarian cancer: a feasibility study.

The tolerability and efficacy of four courses of paclitaxel and ifosfamide plus cisplatin every 3 weeks was evaluated in patients with residual or refractory ovarian cancer. Additionally, supportive haematological effects of recombinant human interleukin 3 (rhIL-3) and recombinant human granulocyte colony-stimulating factor (G-CSF) were studied. Paclitaxel starting dose was 135 mg m(-2) (day 1), with ifosfamide dose 1.2 g m(-2) day(-1) (days 2-4) and cisplatin dose 30 mg m(-2) day(-1) (days 2-4). All 16 patients received 5.0 microg kg(-1) day(-1) G-CSF (days 7-16) and, in addition, eight patients were randomized to receive 10 microg kg(-1) day(-1) rhIL-3 (days 5-9). Paclitaxel and ifosfamide doses were reduced when grade IV haematological toxicity occurred. In the absence of grade IV haematological toxicity and normal recovery of haematopoiesis, paclitaxel dose was escalated. Toxicity was evaluable in 56 courses, with haematological effects in 52. Despite antiemetic treatment, nausea and vomiting (> or = grade I) occurred in 50 courses. Five patients had persisting peripheral neuropathy. Renal and liver function were not affected. Grade IV neutropenia occurred in 12 out of 52 courses, with neutropenic fever in two patients, both of whom died from fatal septicaemia. Grade IV thrombocytopenia without bleeding was observed in 15 courses. Grade IV haematological toxicity was associated with hepatic metastases and concurrent increases in alkaline phosphatase (P <0.001) and gamma-glutamyltransferase (P=0.007). No relation was found between haematological toxicity and pharmacokinetic parameters of paclitaxel. Patients treated with rhIL-3 showed a tendency to a faster platelet recovery (not affecting platelet nadir), and the cisplatin dose intensity was higher (P=0.025). Six of the nine evaluable patients had a tumour response. The overall median progression-free survival was 7 months and the overall mean survival was 13 months. In conclusion, this potentially interesting combination as second-line treatment showed a low tolerability with unexpected mortality, while rhIL-3 administration tended to induce a more rapid platelet recovery.

Adult↗
PubMedDate not supplied

Dose intensity of standard adjuvant CMF with granulocyte colony-stimulating factor for premenopausal patients with node-positive breast cancer.

The effects of granulocyte colony-stimulating factor (G-CSF) on total dose and dose intensity of standard oral adjuvant CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) chemotherapy were studied in premenopausal patients with node-positive breast cancer. Treatment consisted of standard CMF and locoregional radiotherapy (on indication). G-CSF was administered if the leukocyte count recovery was insufficient. Fifty-one patients required no G-CSF ("no cytopenia'), and 50 patients received G-CSF ("G-CSF). Twenty-two patients, however, received no G-CSF support despite insufficient leukocyte recovery ("control'). Following G-CSF, leukocyte recovery was adequate in 83% of the chemotherapy cycles. The proportion of the patients who had a dose intensity > or = 85% was 90% in the "no cytopenia' group, 74% in the "G-CSF' group, and 45% in "control' group (p < 0.05). Leukocyte recovery was adequate in 87% of the chemotherapy cycles in the patients who received radiotherapy as compared with 92% of those in the patients without radiotherapy (p < 0.05). In conclusion an adequate leukocyte recovery after G-CSF was found in 83% of all chemotherapy cycles. The dose intensity of the G-CSF group was higher as compared with controls. The impact of radiotherapy on hematological recovery was significant, but not dependent on G-CSF.

Adult↗