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Biomedical subjects

M Mahlke

Publications and source records attributed to M Mahlke.

10 recordsLinked to original sources
PubMed2007

Role of the progesterone receptor for paclitaxel resistance in primary breast cancer.

Paclitaxel plays an important role in the treatment of primary breast cancer. However, a substantial proportion of patients treated with paclitaxel does not appear to derive any benefit from this therapy. We performed a prospective study using tumour cells isolated from 50 primary breast carcinomas. Sensitivity of primary tumour cells to paclitaxel was determined in a clinically relevant range of concentrations (0.85-27.2 microg ml(-1) paclitaxel) using an ATP assay. Chemosensitivity data were used to study a possible association with immunohistochemically determined oestrogen and progesterone receptor (ER and PR) status, as well as histopathological parameters. Progesterone receptor (PR) mRNA expression was also determined by quantitative RT-PCR. We observed a clear association of the PR status with chemosensitivity to paclitaxel. Higher levels of immunohistochemically detected PR expression correlated with decreased chemosensitivity (P=0.008). Similarly, high levels of PR mRNA expression were associated with decreased paclitaxel chemosensitivity (P=0.007). Cells from carcinomas with T-stages 3 and 4 were less sensitive compared to stages 1 and 2 (P=0.013). Multiple regression analysis identified PR receptor status and T-stage as independent predictors of paclitaxel chemosensitivity, whereas the ER, N-stage, grading and age were not influential. In conclusion, in vitro sensitivity to paclitaxel was higher for PR-negative compared with PR-positive breast carcinoma cells. Thus, PR status should be considered as a possible factor of influence when designing new trials and chemotherapy protocols.

Antineoplastic Agents, Phytogenic↗
PubMed2003

p53 expression and resistance against paclitaxel in patients with metastatic breast cancer.

PURPOSE: Paclitaxel is an important agent in the pharmacological treatment of metastatic breast cancer. Despite its efficacy in selected patients, the majority of patients have a resistance against paclitaxel. The aim of this study was to identify the responding patients and hence prevent the other patients from ineffective treatment. Identifying these patients could spare them an ineffective treatment and could in turn characterize a subgroup of patients with a higher response rate. MATERIAL AND METHODS: Thirty-three patients with metastatic breast cancer received paclitaxel 175 mg/m(2 )either as first- (15 patients) or as second-line (18 patients) treatment. Immunohistochemistry was performed on the blocks of the primary tumors with monoclonal antibodies against p53, HER-2/ neu, P-glycoprotein, Glutathione-S-Transferase-pi, and beta-tubulin II. The expression of those factors was then correlated with the objective response to paclitaxel. RESULTS: Ten of 33 patients had an objective response to treatment. A significant correlation with the objective response was found for the expression of p53. None of the tumors with p53 expression ( n=11) responded to paclitaxel. In contrast, 10 of the 22 patients without p53 expression showed an objective response ( P=0.013). Expression of HER-2/ neu, P-glycoprotein, Glutathione-S-Transferase-pi, and beta-tubulin II did not show a correlation with the response to paclitaxel. CONCLUSION: The immunohistochemical detection of p53 characterizes patients with metastatic breast cancer unlikely to respond to paclitaxel.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Is first-line single-agent mitoxantrone in the treatment of high-risk metastatic breast cancer patients as effective as combination chemotherapy? No difference in survival but higher quality of life were found in a multicenter randomized trial.

BACKGROUND: To determine whether patients with high-risk metastatic breast cancer draw benefit from combination chemotherapy as first-line treatment. PATIENTS AND METHODS: A total of 260 women with measurable metastatic breast cancer fulfilling high-risk criteria, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either mitoxantrone 12 mg/m(2) or the combination of fluorouracil 500 mg/m(2), epirubicin 50 mg/m(2) and cyclophosphamide 500 mg/m(2) (FEC) every 3 weeks. Treatment was continued until complete remission plus two cycles, or until disease progression. In the case of partial remission or stable disease, treatment was stopped after 12 cycles. Second-line treatment was vindesine, mitomycin and prednisolone. Gain from treatment was estimated using a modified Brunner's score composed of time to progression, patients' rating of the treatment benefit, alopecia, vomiting and performance status. RESULTS: After recruitment from 1992 to 1997 and observation from 1997 to 1999, the final evaluation showed that single-agent treatment with mitoxantrone does not differ significantly from combination treatment with FEC in terms of response, objective remission rate, remission duration, time to response, time to best response, time to progression or overall survival. There was, however, a significant difference in gain from treatment using a modified Brunner's score favoring the single-agent treatment arm. There was no evidence that any subgroup would fare better with combination treatment. CONCLUSIONS: No significant difference was detected between the treatment with mitoxantrone as a single agent and the combination of low-dose FEC in terms of response or survival; therefore, the imperative of the necessity of first-line combination chemotherapy for patients with high-risk metastatic breast cancer may be questioned. Since toxicity and quality of life score favored the single-agent mitoxantrone treatment arm, this treatment may be offered to patients preferring quality of life to a potential small prolongation of survival.

Adult↗
PubMed1996

[High dose chemotherapy in treatment of breast carcinoma: current status and limits of this method of therapy].

Current Status and Limits: High-dose chemotherapy with autologous haematopoietic stem cell rescue has become in recent years a widely accepted therapeutic modality for advanced stage breast cancer in North America. The emergence of modern supportive measures like peripheral blood stem cell rescue has significantly decreased the toxicity and cost of high-dose chemotherapy. The rationale for use of escalated chemotherapy doses in breast cancer is the establishment of a dose-response relationship, with higher doses producing increased response rates in preclinical studies as well as in clinical trials. The dose limiting myelotoxicity of several active agents in breast cancer can only be overcome by rescue with previously cryopreserved autologous haematopoietic stem cells. Two phase II clinical trials with high-dose chemotherapy as adjuvant measure in high-risk breast cancer patients with multiple positive axillary nodes have been published so far. Disease-free survival is these 2 studies was 71 and 84% after 5 and 3 years of follow-up, and hence significantly longer compared to historic controls. Randomised phase III trials are urgently needed to confirm these promising results. Several reports of high-dose chemotherapy in disseminated breast cancer have been published so far. Most of these studies could establish a high response rate of about 70%, half of which were complete responses. However, most tumour regressions were short lived and overall survival was not prolonged compared with historic controls. Therefore, high-dose chemotherapy cannot be recommended for disseminated breast cancer patients outside of innovative clinical trials. To improve on the results in disseminated breast cancer patients the use of repeated cycles of high dose chemotherapy or the value of tumour cell purging of the stem cell product are being currently explored by different groups. In general, breast cancer patients should only be treated with high dose chemotherapy in context with a clinical trial.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[Persistent granulocytosis and hyperuricemia after a single G-CSF injection (Filgrastim) in treatment of chemotherapy-induced myelosuppression in metastatic breast carcinoma].

We report about a patient with metastatic breast cancer treated with chemotherapy regime (CMF), who developed a febril leukopenia as well as a hyperuricemia. A single subcutaneous application of 300 micrograms Filgrastim led to a severe overstimulation with leukocytosis of max. 50,000 for about 8 days and hyperuricemia.

Aged↗
PubMed1991

[Intra-arterial preoperative chemotherapy of advanced cervix cancer].

Three patients suffering from very advanced primary cancers of the cervix uteri (FIGO II B or III B) were treated. By preoperative selective perfusion of both uterine arteries, using cis-platinum alone, a distinct reduction of the tumour volume was achieved. This was demonstrated clinically and also by CAT scan and NMR technique. The elevated serum CEA and SCC levels decreased to normal values. The histomorphology of the Wertheim-Meigs specimens revealed no tumour invasion of the initially infiltrated parametria. This treatment modality has been developed to minimise the toxic side effects of the inductive (neo-adjuvant) chemotherapy for cervical cancers.

Adult↗
PubMed1989

[Surgical treatment of vulvar cancer and plastic reconstruction of vulvar defects].

In recent years sufficient scientific and clinical data have become available to establish an individualized treatment plan for each patient suffering from vulvar carcinoma. Organ-preserving operations are strictly confined to "early cases" as described by a careful histopathology of the primary lesion. The high perioperative morbidity and the bad cosmetic results of extended radical vulvectomy are definitely improved by additional plastic reconstructive procedures. Neoadjuvant chemotherapy probably results in a better survival rate in lymph node positive patients.

Female↗
PubMed1985

Oral high-dose medroxyprogesterone acetate (MPA) treatment: cortisol/MPA serum profiles in relation to breast cancer regression.

Medroxyprogesterone acetate (MPA), a potent synthetic progestin, has been widely used in the hormonal treatment of advanced breast cancer, but presently with varying dose schedules. The availability of a sensitive RIA-method for determination of serum MPA has stimulated the research on MPA serum levels in patients after repeated MPA administration. The aim of this study was to assay blood level profiles of MPA as well as of cortisol during repeated high-dose orally administered MPA. 34 patients with metastatic breast cancer were enrolled in this study. 12 patients died already within the first 4 weeks of MPA treatment due to multiple metastases. The dosage regimen based on the daily oral administration of 1,000 mg MPA suspension. During MPA treatment, a decrease of cortisol serum levels was observed in nearly all patients. Within the observation time of 8 months out of 22 evaluable cases 18.2% responded to the therapy (complete and partial response). No change was observed in 36.4% and progression in 45.5% of the patients. Within the remission (complete and partial) group, a good correlation between constant MPA serum levels above 150 ng/ml and remission was observed. But in the groups with no change and progression no such correlation could be observed.

Administration, Oral↗
PubMed1985

[Expanded possibilities of the treatment of vulvar cancer by plastic reconstructive procedures].

By means of 5 examples it is demonstrated, in which way large defects in the vulvar region can be covered plastically. Dependent on the situation a simple local tissue displacement (according to the principle of transpositionplasty) or a myocutaneous flapplasty using the m. tensor fasciae latae or the m. gluteus maximus will be favourable. These expanded possibilities for treatment of carcinoma of the vulva by own experiences are so convincing, that their application is recommendable on a larger scale and will be an enrichment in operative gynaecology. The techniques described can be used by gynaecologists with appropriate operative and clinical experience.

Aged↗