Biomedical subjects
Publications and source records attributed to S Seeber.
Fourteen patients with localized Ewing's sarcoma were treated with radiation therapy to the involved bone and systemic chemotherapy. Nine patients remained free of disease for a median follow-up period of 3 years. The actuarial 5-year disease-free survival rate is 60%.
Improved chemotherapeutic results have been obtained recently with combinations of 5-fluorouracil, adriamycin, and mitomycin or a nitrosourea derivative. The response rates have been raised to 40%, and the median survival rate of responding patients has been increased to over 12 months. Regional disease should be treated by chemotherapy plus irradiation. Patients with curative resections are receiving adjuvant chemotherapy with improved regimens in various ongoing studies.
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From a single wild-type strain of Ehrlich ascites tumor, sublines resistant to daunorubicin, etoposide, and cis-diamminedichloroplatinum(II) have been developed in vivo. Different levels of resistance were achieved after 4 to 8 months for anthracyclines (greater than 32-fold), cis-diamminedichloroplatinum(II) (4-fold), and etoposide (greater than 6-fold). Anthracycline resistance was associated with decreased nuclear steady-state concentration of anthracyclines, increased content of high-molecular-weight membrane glycoproteins, and glucose-dependent drug extrusion after metabolic blockade with sodium azide. A similar "pump" system which was apparently not drug specific was also documented in etoposide resistance. Resistance towards cis-diamminedichloroplatinum(II) was accompanied by decreased cis-diamminedichloroplatinum(II)-induced DNA damage in vitro when proteinase K-resistant interstrand cross-links were measured by alkaline elution. Parallel in vivo studies revealed cross-resistance of various degrees among a number of anthracycline analogs, complete cross-resistance among daunorubicin, doxorubicin, and 4'-(9-acridinylamino)methanesulfon-M-anisidine (amsacrine), and partial cross-resistance between daunorubicin and etoposide. However, cis-diamminedichloroplatinum(II) was curative in anthracycline- and etoposide-resistant cells, as daunorubicin and etoposide were curative in acquired resistance towards cis-diamminedichloroplatinum(II). cis-Diamminedichloroplatinum(II) resistance was also overcome by the derivative 1,2,diaminocyclohexylplatinum malonate. The Vinca alkaloid vindesine, although only marginally active in the control tumor, was highly active in cells selected for cis-diamminedichloroplatinum(II) resistance. These in vivo patterns of cross-resistance and collateral sensitivity may be related to observations in clinical chemotherapy.
Cancer chemotherapeutic agents and antimicrobial antibiotics are often given concomitantly. Cisplatin, which has become increasingly important in cancer treatment, has shown nephrotoxicity as a dose-limiting feature. The alpha-carboxy-penicillin ticarcillin (tc) has a wide spectrum of antimicrobial activity, especially against Pseudomonas. The plasma half-life of tc is correlated with renal function. The combined use of cisplatin (20 mg/m2, days 1-5) and tc (3 X 5 g/24 h, days 1-5) with renal protection by vigorous hydration (2400 ml of 0.9% NaCl/24 h continuous infusion, days 1-5) in a group of 12 cancer patients did not alter the BUN and creatinine serum levels. The mean serum concentration of tc, which was monitored in a patient 15, 30, and 45 min after injection of 5 g on 4 consecutive days together with cisplatin, did not differ from the levels of tc reported when used without concomitant cisplatin therapy. Thus these preliminary data show that the pharmacology of tc may not be altered significantly when applied together with cisplatin and that cumulative nephrotoxicity must not be expected with this combination when sufficient hydration is used.
Sequential chemotherapy with vinblastin and bleomycin, as well as adriamycin and cis-platin, was administered to 29 patients with disseminated malignant testicular teratoma. In order to intensify the induction phase, the intervals between drug administrations were individually shortened, with the next course of treatment following directly after the phase of critical leucocyte depression. This method was pursued over four courses of chemotherapy without dose reduction, followed by courses of chemotherapy in a conventional three-weekly rhythm. A response was obtained in 28 patients, 18 of them achieving complete remission. Taking into consideration unfavourable prognostic factors in the treatment group, this result is better than after the same chemotherapy at three-weekly intervals. Induction treatment adapted to leucocyte response carries with it the risk of higher toxicity, but this would seem to be acceptable in view of the improved long-term prognosis. This or similar intensification of the first treatment phase, for a long time used with leukaemias, could also be considered in the management of various chemotherapy-sensitive solid tumours, especially in younger patients.
43 patients with metastasizing sarcomas were treated with a combination of either vincristin, adriamycin and cis-platinum (n = 21) or ifosfamide and cis-platinum at three weeks' intervals in each case. Ten patients responded to the first combination and nine to the second combination with objective tumor regression. Particularly the latter result is remarkable since 16 of the 22 patients had already been pretreated with combinations containing adriamycin. Obviously the combination of ifosfamide and cis-platinum is a promising alternative in metastasizing sarcomas of the bones and soft tissue, especially if the CYVADIC combination--which is often regarded as standard treatment--remained unsuccessful. This has no bearing on additional surgical measures or on radiotherapy which may be necessary in some patients.
We present the case of a 39-year-old man with Klinefelter's syndrome and a metastatic Leydig cell carcinoma in whom autonomous cortisol production induced by the interstitial cell tumor was found. Apart from the Cushing's syndrome the endocrine activity of the tumor was demonstrated by the secretion of estradiol, estrone, alkaline phosphatase, and testosterone. This is, to our knowledge, the first description of a Cushing's syndrome not caused via ACTH production but directly induced by ectopic steroid production. While being resistent to chemotherapy and radiation, the tumor responded favorably to treatment with o,p'-DDD. The reduction of tumor size was accompanied by a continuous decrease of serum markers. The etiology of the tumor is discussed in the light of the hormonal derangement caused by the genetic abnormality of Klinefelter's syndrome.
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Sixty-two patients with metastatic soft tissue sarcomas of various histological types were treated with Cyvadic. No chemotherapy had been given previously. Complete remission (CR) was obtained in 10% and complete plus partial remission (PR) in 20% of the patients. Mean duration of CR was 25 months, that of PR 2.5 months. Median survival time of responders was 28 months, that of nonresponders 14 months. Chemotherapy with a combination of ifosfamide plus cisplatin given to patients with primary or secondary resistance to Cyvadic led to CR + PR in 50% of the patients.
Between 1974 and 1979 a total of 344 patients with testicular teratomas were treated at the West German Tumor Center, Essen. Brain metastases were encountered in 16 patients by means of neurologic symptoms as well as scintigraphy and computerized tomography. Cerebral involvement was closely related to preexistent lung metastases (n = 162) and the risk appeared to increase with the duration of pulmonal disease amounting to about 10% (16/162) in this group. Radiotherapy was the treatment of choice and produced objective and subjective improvement in 13 of 16 cases. Thus, long-term prognosis of patients with brain metastases was mainly determined by the preexistent metastatic involvement of the lungs.
Based on new drugs, new combinations, earlier onset of treatment and aggressive doses in the induction phase chemotherapeutic results in advanced cancer have been improved within the last decade. The present review presents the currently available realistic results obtained with both curative and palliative chemotherapy. In addition, the concepts of preoperative ("debulking") chemotherapy and of adjuvant chemotherapy are described for the adequate clinical indications. Finally, guidelines for chemotherapeutic measures in elderly patients are presented.
83 patients with small-cell bronchial carcinomas were treated with a combination of cytostatic chemotherapy ("ACO II" = adriamycine, cyclophosphamide, vincristine) and irradiation of the mediastinum, the tumor umbra and the affected hilum with a focal dose of 30 Gy administered within a period of three to four weeks. During the same period, those patients presenting the favorable initial stage "limited disease" (LD) were additionally submitted to a prophylactic total brain irradiation with a dose of 30 Gy. 42 among 55 patients of stage LD had a complete remission. Among these 42 patients, fourteen had an intrathoracic recurrence, nine of them within the irradiation field. A cerebral recurrence after prophylactic brain irradiation was found in five of 42 cases. The conclusion is drawn that the irradiation dose which has to be administered into little intrathoracic fields must be increased. A dose of 45 Gy within 4 1/2 weeks is desirable. It seems that a prophylactic brain irradiation is only efficient in patients with a favorable prognosis (LD, CR).
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