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H van Veelen

Publications and source records attributed to H van Veelen.

14 recordsLinked to original sources
PubMed2000

[Adjuvant systemic therapy for patients with resectable breast cancer: guideline from the Dutch National Breast Cancer Platform and the Dutch Society for Medical Oncology].

There is an abundance of evidence that adjuvant systemic therapy with chemotherapy or endocrine therapy results in better survival for all patients with resectable breast cancer. The absolute 10-year survival advantage however varies for the different patient groups. Therefore, for each individual patient the choice of adjuvant therapy must take into account the potential benefits and the possible side effects. A group of medical oncologists from the Dutch National Breast Cancer Platform (NABON) and the Dutch Society for Medical Oncology (NVMO) prepared a guideline for the treatment of patients with early resectable breast cancer. The criterium for choosing adjuvant systemic therapy for the individual patient is an expected increase in 10-year survival of 5% or more. In the guideline a difference is made between patients with and without axillary lymph node metastasis. In patients with axillary lymph node metastasis the choice for adjuvant systemic therapy depends on the following prognostic factors: menopausal status, age, and the presence of estrogen and progesterone receptors in the tumour. In patients without axillary lymph node metastasis the choice depends also on the following prognostic factors: the size of the tumour, the mitotic activity index, or the histopathologic grade of differentiation.

Adult↗
PubMed1995

An extra gonadal non-gestational choriocarcinoma in a woman treated for an endometrial carcinoma.

A patient was presented with a non-gestational non-gonadal choriocarcinoma and hyperthyroidism. Five years earlier, at the age of 36, she underwent an abdominal hysterectomy with bilateral adnexectomy for endometrial carcinoma. Despite intensive treatment with multiple chemotherapy the patient died. We concluded that this non-gestational, non-gonadal choriocarcinoma was a recurrence of her previous endometrial carcinoma or a new extra (non) gonadal germcell tumor with choriocarcinoma.

Adenocarcinoma, Papillary↗
PubMed1990

A randomized comparison of megestrol acetate (MA) and medroxyprogesterone acetate (MPA) in patients with advanced breast cancer.

The efficacy and side-effects of megestrol acetate and medroxyprogesterone acetate in postmenopausal patients with advanced breast cancer were compared in a prospectively randomized study. The dosage of MA was 2 X 80 mg p.o. or MPA 2 X 500 mg p.o. daily, given as a secondary hormonal treatment, mostly after previous treatment with tamoxifen. Ninety-eight patients entered the study and 92 were evaluable for effect, 48 patients on MA and 44 on MPA. Age, main tumor site and prior treatment were not different, but there was a preponderance of ER-negative tumors in the MA group. Responses appeared to be more frequent in the MPA-treated group (25% vs. 43%), predominantly in bone lesions, 12% for MA and 45% for MPA. Median progression-free survival was comparable, 15 vs. 10 months, and overall survival was not different (20 vs. 16 months). Toxicity was frequent, occurring in 83% vs. 74% of patients: increased appetite, nausea and dizziness in more than 20%, and a preponderance of pyrosis and breathlessness on MA and hot flashes, sweating and tremors on MPA. Cushingoid symptoms were present in about a quarter of the patients treated for more than 3 months. The occurrence of thrombo-embolic episodes and cardiovascular events was evenly distributed. Patients on MPA had more often increase in body weight, systolic blood pressure and serum creatinine than those treated with MA. It is concluded that MPA may be more effective for treatment of bone metastases, at the expense of more progestational side-effects. The occurrence of Cushingoid effects is frequent but similar in both arms, while the incidence of cardiovascular or thrombo-embolic events cannot be related to the use of either compound.

Aged↗
PubMed1990

Adrenal steroids as parameters of the bioavailability of MA and MPA.

Serum levels of cortisol (C), androstenedione (A), dehydroepiandrosterone (D), estrone (E1) and estradiol (E2) were chosen as parameters to compare the bioavailability of megestrol acetate (MA) and medroxyprogesterone acetate (MPA) in postmenopausal patients with advanced breast cancer. In 36 patients randomized to MPA, the levels of A (13% vs. 19%) and C (6% vs. 8%) were slightly lower than in 36 patients on MA, but D-levels (68% vs. 59%) and E1 or E2, were similar. The correlation between baseline C and A disappeared during treatment. Treatment levels of E1 and E2 were correlated. There was no correlation between individual drug levels and any steroid, indicating a maximal suppression. After ingestion of a single dose of MA or MPA, peak levels were found after 2-3 h for MA and 3-4 h for MPA. Four hours after ingestion, the levels of A and C were similar, 40-60% of baseline values, while D levels remained unaltered. Doubling the dose of either drug did not enhance hormone suppression, indicating that the drug dosage is maximally suppressive. In conclusion, although the median serum MA levels are double those of MPA, suppression of A, C and D is usually similar, with corresponding estrogen levels, demonstrating a comparable and maximal bioavailability. Higher dosages of MA or MPA will not increase their pharmacological effects any further.

Adrenal Cortex Hormones↗
PubMed1986

Oral high-dose medroxyprogesterone acetate versus tamoxifen. A randomized crossover trial in postmenopausal patients with advanced breast cancer.

In a prospective randomized multicenter study in previously untreated postmenopausal patients with advanced breast cancer, the response to treatment with oral medroxyprogesterone acetate (MPA) 300 mg three times daily was compared with tamoxifen (TAM) 20 mg twice daily. Of 61 patients treated with MPA, 27 (44%) had a partial or complete remission, 6 showed no change, and 28 had progressive disease. Of 68 patients treated with TAM, 24 (35%) showed a remission, 15 no change, and 29 progression. The difference in response rate is not significant. However, 11 of 25 patients with osseous metastases as predominant site, responded to MPA and 7 of 31 to TAM (P = 0.05). Moreover, in patients older than age 70 years, 13 of 26 responded to MPA and 6 of 31 to TAM (P less than 0.05). Median duration of remission of all patients in the MPA arm was 17 months and in the TAM arm, 23 months (not significant). Median survival was 20 months for MPA and 26 months for TAM (not significant). After cross-over from TAM to MPA 8 of 31 patients responded and after cross-over from MPA to TAM, no response was seen in 27 patients. These data indicate that the response rate and duration to MPA and TAM are comparable, except in patients with osseous metastases and in patients older than age 70 years. MPA has more side effects, but seems to be more effective after cross-over, and may thus be reserved for second-line treatment.

Aged↗
PubMed1985

Specific and sensitive determination of medroxyprogesterone acetate in human serum by gas chromatography-mass spectrometry.

The mass fragmentographic determination of medroxyprogesterone acetate (MPA) in serum, using as internal standard medroxyprogesterone propionate (MPP) synthesized from MPA, is described. After addition of MPP, the sera are extracted on Sep-Pak C18 cartridges and MPA and MPP are detected as their respective 3-enol trifluoroacyl esters. Serum samples from 84 patients with breast cancer, daily receiving MPA orally, were determined showing a large variation in MPA concentrations (4-349 ng/ml). Our proposed gas chromatographic-mass spectrometric (GC-MS) method, which can be considered as a reference, was compared with a radioimmunoassay (RIA) method showing a correlation coefficient of 0.73 (n = 69; p much less than 0.001). The assay was also used to determine sequential serum levels of patients receiving a single oral dose of MPA. With only minor adjustments, the GC-MS method allows the determination of serum concentrations of related steroids such as megestrol acetate and cyproterone acetate.

Biological Availability↗
PubMed1985

Mechanism of adrenal suppression by high-dose medroxyprogesterone acetate in breast cancer patients.

To investigate the mechanism of adrenal suppression by high-dose MPA, we performed direct and indirect stimulation tests in postmenopausal women with disseminated breast cancer who were receiving MPA and in a postmenopausal breast cancer control group. A partial adrenal insufficiency was found during Synacthen stimulation, confirmed by a slight increase of 11-desoxycortisol after metyrapone, despite a sufficient rise in ACTH levels. Peak levels of androstenedione and 17-OH progesterone after Synacthen correlated with those after metyrapone. Peak cortisol levels after Synacthen also correlated with the sum of cortisol and 11-desoxycortisol values after metyrapone, indicating the presence of a maximum adrenal response and a sufficient rise of endogenous ACTH after metyrapone. As the peak levels of cortisol and androstenedione were highly correlated with baseline values, a short Synacthen stimulation test may give a good indication as to whether adrenal suppression by MPA is adequate. The adrenal androgen androstenedione is the precursor of the main postmenopausal oestrogen, oestrone. In this way, adrenal suppression may constitute an important therapeutic effect of high-dose MPA.

17-alpha-Hydroxyprogesterone↗
PubMed1985

Endocrine effects of medroxyprogesterone acetate: relation between plasma levels and suppression of adrenal steroids in patients with breast cancer.

The elimination of adrenal steroids by adrenalectomy or medical treatment has been one of the mainstays in the palliative treatment of patients with disseminated breast cancer. Recently, the effects of progestins on adrenal function has become the subject of renewed interest. To find a relation between plasma levels of medroxyprogesterone acetate (MPA) and adrenal suppression in breast cancer patients, we compared a group of 41 postmenopausal patients with disseminated or inoperable breast cancer, treated with oral MPA, with a control group of 28 postmenopausal breast cancer patients without treatment. To obtain MPA plasma levels in the lower range, 13 patients initially received 300 mg of MPA daily (Group 1), six of whom were subsequently treated with 600 mg (Group 2). Group 3 comprised 37 patients treated with 900 mg of MPA. All of the parameters studied varied widely. Only in Group 3 patients were the MPA levels higher and the levels of cortisol, androstenedione, DHAS, and estrone lower than those in Group 1 patients. All steroid levels in Group 3 were significantly below control values. Considering all data, a negative but weak correlation was found between MPA levels and cortisol (R = -0.55), androstenedione (R = -0.58), and dehydro-epi-androsterone sulfate (R = -0.40), but not for MPA and estrone, indicating better adrenal suppression by higher MPA dosage and plasma levels. However, suppressed cortisol concentrations did not predict sufficient MPA dosage in all patients because low cortisol was not always associated with high MPA levels. A positive relation existed between the levels of androstenedione and estrone, which shows that suppression of these adrenal androgens may result in suppression of plasma estrone. This may be of additional therapeutic benefit in breast cancer patients.

Adrenal Glands↗
PubMed1984

Adrenal suppression by oral high-dose medroxyprogesterone acetate in breast cancer patients.

The effects of oral MPA, 300 mg t.i.d., on adrenal function in postmenopausal patients with disseminated breast cancer were evaluated. The levels of serum cortisol, ACTH, androstenedione, DHEA-S, LH, FSH, GH, and prolactin in 22 patients receiving MPA were compared with those in another group of 28 postmenopausal patients in whom levels were measured before treatment. The median morning cortisol level was 70, 10-465 nmol/l (controls 395, range 155-785 nmol/l), median androstenedione 1.09, range 0.55-3.10 nmol/l (controls 3.75, range 1.23-9.81 nmol/l), and median DHEA-S 555, range 55-1,300 nmol/l (controls 2,440, range 1,015-6,340 nmol/l). No appreciable change in ACTH levels was found. Gonadotropins were also markedly suppressed. The median LH level was 4.3 (range 0.8-18) U/l, as against 83 (range 19-116) U/l in controls. The median FSH level was 7.2 (range 0.5-27) U/l, as against 71 (range 12-262) U/l in controls. Prolactin and GH levels remained largely unchanged. The suppression of androstenedione synthesis, the main precursor of postmenopausal estrogens, may represent the major therapeutic effect of high-dose MPA in postmenopausal patients with breast cancer.

Adrenocorticotropic Hormone↗
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↗