J.-H. Beyer

Treatment of polycythemia vera by isovolemic large-volume erythrocytapheresis

SummaryExcess red blood cells (RBC) in patients with polycythemia vera (PV) are usually removed by repeated phlebotomy. In order to improve the efficacy of this treatment, we used isovolemic large-volume erythrocytapheresis (EA) by a cell separator. A retrospective analysis of our experience with 69 PV patients (206 EA procedures) is reported. EA induced a rapid, well-tolerated, and long-lasting reduction of Hct, Hb, and RBC counts, as well as an immediate disappearance or reduction of clinical symptoms of PV, while tissue oxygen tension — as measured in 8 patients — increased. Hct was reduced by EA from 56.8% ±5.6% to 41.9% ±6.6%, Hb from 17.5±2.3 to 12.7±2.4 g%, RBC counts from 7.±0.9 to 5.4±0.9×106/mm3. The mean volume of the apherisate was 1410±418 ml, (mean Hct 79.7%±9.3%), and the actual RBC volume removed 1113±367 ml. The isovolemic procedure was well tolerated and the acceptance by patients seemed to be better than with repeated phlebotomy. In 21 patients whose Hct values (Hct before and after EA 58%±5.7% and 41.5%±4.9%) were regularly followed after EA the mean period with Hct<50% after a single EA procedure was 6.1±4.1 months (median, 6); in 14 out of these 21 patients a Hct of <43% after EA was reached and their mean period with Hct<50% after EA was 7.6±4.0 months (median, 7.5). For three patients this period was 11, 13, and 15 months, respectively. In our experience large-volume isovolemic EA is a feasible, very effective, and welltolerated alternative treatment modality for PV patients. It may be superior to repeated phlebotomy, especially for patients with excessively increased RBC mass. Only a controlled prospective trial can answer the question, whether EA, due to its rapid effect and due to the long-lasting lower RBC mass, leads to a lower rate of thromboembolic events, and whether EA may delay the necessity for treatment of PV by cytotoxic drugs or P32.

Tumor-associated antigens in effusions of malignant and benign origin

SummaryWe determined the concentration and effusion/serum ratio of mucin-like carcinoma-associated antigen (MCA) in comparison to carcinoembryonic antigen, carbohydrate antigen 19-9, cancer antigen 125, and cancer antigen 15-3 in 80 sera and 99 effusions from 64 patients with histologically confirmed malignancies (4 patients out of this group showed various effusions simultaneously, which were analyzed separately) and 31 patients with various nonneoplastic diseases. Tumor cells were detected by cytological examination in 41 effusions (60.3%) from patients with neoplastic diseases, while in another 27 cases this method failed to demonstrate the malignant origin of the effusion. Of the cytological “positive” malignant effusions 90% were also correctly identified by an elevated MCA concentration at a cutoff level of 10 U/ml, whereas only one effusion of benign origin (3%) showed a slightly elevated MCA concentration of 10.5 U/ml. In 33% of cytologically “negative” effusions of patients with neoplastic diseases, the MCA concentration was also elevated, with a maximum of 453 U/ml. Increased MCA levels in cytologically confirmed malignant effusions were not restricted to metastatic breast cancer. All 17 cytologically “positive” “non-breast cancer” effusions were correctly identified by their MCA concentrations. None of the other tumor markers reached this high sensitivity at the same level of specificity. The ratio of effusion/serum concentration of all tumor markers as well as the concentration of cancer antigen 125 in effusions was of little diagnostic value. Our results indicate that the MCA concentration in an effusion correlates very closely with its malignant origin and is superior to all the other antigens tested. Accordingly, the concurrent MCA determination could improve the diagnostic accuracy of the cytological examination of effusions.

Intra-Arterial Perfusion Therapy with 5-Fluorouracil In Patients with Metastatic Colorectal Carcinoma and Intractable Pelvic Pain

In a phase-II trial, 18 patients with intractable pelvic and perineal pain caused by local recurrent and/or metastatic colorectal carcinoma resistant to combinations of analgesics, systemic cytostatic chemotherapy and/or radiation were treated with intra-arterial perfusion therapy using 15-30 mg 5-FU/kg body wt./day for 1-5 days. Of 18 patients, ten achieved complete pain relief for 3-32 weeks (mean, 15.7 weeks); after the perfusion therapy eight used less than 50% of the amount of analgesics required before treatment; one patient had only a minor response; two patients were treated unsuccessfully. Side effects were mild and controllable. One patient died subsequent to arterial embolism in the leg where the catheter was placed; pelvic perfusion therefore appears risky in patients with severe arteriosclerosis.

High-Dose Epirubicin in Combination with Cyclophosphamide (HD-EC) in Advanced Breast Cancer: Final Results of a Dose Finding Study and Phase II Trial

In the dose finding study we were able to demonstrate that an increase of the epirubicin dose to 120 mg/m2 in combination with cyclophosphamide (600 mg/m2) is possible. The phase II trial had to check the efficacy and the toxicity of this combination with a therapy interval of 21 days. 34 patients with metastatic breast cancer previously not treated with chemotherapy for metastatic disease entered this phase II trial, which tested the efficacy and toxicity of the chemotherapy combination epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 (HD-EC regimen) i.v. every three weeks. Excluded from the trial were patients at risk of anthracycline toxicity and those with bone or brain metastases. Results compare favourably with best data reported in the literature for chemotherapy of metastatic breast cancer: overall remission rates of 73% (35% CR, 38% PR), median TTP of 58 weeks for CR (range 32-168 weeks) and 52 weeks for the PR group (range 24-110 weeks); median survival time for CR 71+ weeks (range 52-196+), for PR 74+ weeks (range 40-134+ weeks). No therapy was given for remission maintenance after a stable remission was obtained. This results in a very favourable ratio of time with chemotherapy to maintenance time without chemotherapy, which is 10 weeks/62 weeks for CR and 12 weeks/49 weeks for PR. Evidence of tumor remission was found in 80% of the patients who already responded to chemotherapy after the first cycle. The early onset of tumor response as well as the short induction chemotherapy period necessary to obtain best response are considered major advantages of the HD-EC regimen.

Zweite Zwischenauswertung einer Chemotherapiestudie an Patienten mit Plattenepithelkarzinomen des Kopf-Hals-Bereiches

52 Patienten wurden entweder mit cis-DDP und Bleomycin (Arm A) oder mit Methotrexat und Vindesin (Arm B) behandelt. Bei Resistenz wurde auf das alternative Therapieregime uberfuhrt. Die Ergebnisse zei

In vitro adsorption of colon cancer sera over staphylococcus protein a: lymphocyte stimulation by leakage of adsorbance

SummarySerum factors may be responsible for reduced host-anti-tumor defence. Although there is still confusion about their origin, attempts have been made to immobilize serum components by Protein A columns as a therapeutic modality. In our study the in vitro adsorption of 90% of the IgG from cancer sera on “immobilized protein A” did not influence the inhibitory serum activity as measured in a mixed lymphocyte culture. Therefore, IgG or immune complexes do not seem to be the suppressive serum factor in patients with advanced colorectal carcinoma. There is evidence for leakage of small amounts of protein A from the columns which have immunostimulatory activity. Perhaps this may explain necrosis after a therapeutic immunoadsorption.

Alterations of lymphocyte subpopulations by chemotherapy and chemoimmunotherapy (Thymostimulin) in patients with head and neck cancer

1/6, duration 28 months. After this period, in addition to local recurrence there was progress of the lung metastases. In three pts the primary tumor was subtotally resected. These patients presented no measurable tumor parameter and so far after i0 months observation there is no evidence of recurrence. Conclusions: Preliminary results of this combination therapy for ACC of the head and neck region show a high

Chemotherapy of squamous head and neck cancer: a prospective randomized trial comparing cis-platinum and bleomycin with methotrexate and vindesine.

A series of 79 patients with locally inoperable squamous cell carcinoma of the head and neck region were treated from June 1979 to December 1982. The status of inoperability was based on a surgical evaluation indicating that the tumor and/or regional nodes could not be totally resected with curative intent. The aim of this study was to compare an aggressive regimen against a mild one.

Zytostatische Therapie von fortgeschrittenen Plattenepithelkarzinomen des Kopf-Hals-Bereiches

In einer randomisierten Studie wurden 79 Patienten entweder mit cis-DDP 3 mg/kg i.v. Tag 1 und Bleomycin 15 mg/m2 i.v. kontinuierlich Tag 2–5 (Arm A) oder weniger aggressiv mit Methotrexat

Cisplatin (DDP) and etoposide (VP-16) as primary chemotherapy in patients with squamous cell carcinoma of the head and neck region (SCC-HN)

1/6, duration 28 months. After this period, in addition to local recurrence there was progress of the lung metastases. In three pts the primary tumor was subtotally resected. These patients presented no measurable tumor parameter and so far after i0 months observation there is no evidence of recurrence. Conclusions: Preliminary results of this combination therapy for ACC of the head and neck region show a high