Palliation by intratumoral infiltration with natural interferon-beta.

BACKGROUND: Curative approaches to tumor therapy have achieved greater importance through new developments such as cytostatic agents and their combination with other therapy concepts, but for the majority of tumor patients only palliative therapy is possible. Size or location of tumor manifestations can result in severe discomfort for patients, in some cases even in a reduction of functionality. PATIENTS AND METHODS: For the purpose of this study, a total of 55 patients with a variety of advanced malignant diseases nonresponding or progressive under radio- and/or chemotherapy were treated by intratumoral injection of natural human fibroblast interferon (nIFN-beta). nIFN-beta was administered intralesionally 3 times per week for at least 4 weeks at doses of 2-8 MIU, depending on tumor size. Local tumor response was observed over a median follow-up period of 18 weeks. RESULTS: In 37 patients (67%) a complete or partial remission of the local tumor manifestation was achieved. Survival times of these patients were improved compared with those of patients without local tumor remission. 16 patients without significant change of tumor volume benefited from the palliative (extensive analgesic) effect of the nIFN-beta therapy. During treatment, none of the patients showed a progression of the locally treated tumor, even when the basic malignant disease progressed. The side effects of the nIFN-beta therapy were tolerable, and no patient discontinued therapy. CONCLUSION: From these observations, intralesional nIFN-beta therapy of malignant tumors appears to be a useful palliative addition to radio- and/or chemotherapy with the aim of local control of tumor growth.

Undifferentiated (embryonal) sarcoma of the liver in an adult patient with metastasis of the heart and brain.

A 26-year-old woman with a tumor of the left liver lobe was admitted to the hospital. After incomplete resection of the tumor and histological diagnosis of an undifferentiated (embryonal) sarcoma of the liver a combination chemotherapy with ifosfamide and epidoxorubicine was started. 11 months later brain metastases were diagnosed. Routine ultrasound examination of the heart disclosed a pericardial tumor infiltrating the left atrium of the heart. After radiation therapy of the brain metastases the patient was treated with two cycles of high-dose ifosfamide and epidoxorubicin. Two years after diagnosis the patient developed signs of cardiac failure and died. Postmortem autopsy confirmed the local recurrence of the liver neoplasm and revealed its continuous spread to the pericardium via the diaphragm and infiltration of the left atrium.

[The palliative treatment of primary hepatocellular carcinoma by chemoembolization]. / Palliative Behandlung des primären Leberzellkarzinoms mit Chemoembolisation.

16 patients (12 men, 4 women; mean age 62.8 +/- 9.8 years) with inoperable advanced hepatocellular carcinoma were treated palliatively by chemoembolization. 50 mg/m2 epirubicin, 30 mg/m2 cisplatin, 8 ml fatty acid ethyl ester of iodinated papaver oil and 10 ml nonionic contrast medium were injected under fluoroscopy into the proper hepatic artery. Partial remission was achieved in 10 patients after a median of 4 months. In 4 patients there was no change in the morphological and biochemical findings, in two others the tumour progressed, i.e. an overall response rate of 62.5%. The median survival time was 9 months. There were no serious complications ascribable to the treatment. Chemoembolization is a palliative treatment with few side effects which can also be effective in prolonging survival time in advanced hepatocellular carcinoma.

[The results of the chemoembolization of advanced hepatocellular carcinomas. The effect on the survival times, morphological findings and tumor markers]. / Ergebnisse der Chemoembolisation fortgeschrittener Leberzellkarzinome. Einfluss auf Uberlebenszeiten, morphologische Befunde und Tumormarker.

Chemoembolization is a well-recognized therapeutic procedure in the treatment of stage I and stage II hepatocellular carcinoma (HCC). Until now it is rarely used in the treatment of stage III HCC. In a prospective study we analysed the efficacy and the side effects of chemoembolization in 16 patients with stage III HCC. Chemoembolization was performed with an emulsion of lipiodol, 4-epirubicin and cisplatinum. All patients tolerated the treatment without remarkable complications. With 9 months the median survival rate was considerable higher than the survival rate of untreated patients and of patients treated with systemic chemotherapy or with local perfusion.

Adjuvant chemotherapy of metastatic stage II nonseminomatous testis tumor.

In a prospective randomized trial, 225 patients with stage IIB nonseminomatous testis tumor after radical retroperitoneal lymph node dissection received 2 versus 4 courses (arms 1 and 2, respectively) of adjuvant chemotherapy with cis-platinum, vinblastine and bleomycin. With a median followup of 43 months, a total of 7 relapses occurred; 6 in arm 1 and 1 in arm 2. Three patients died: 2 during adjuvant chemotherapy and 1 of progressive disease. The difference in relapse rates between arms 1 and 2 is not statistically significant. Patient compliance differed: chemotherapy was administered according to protocol in 83% and 50% of the cases in arms 1 and 2, respectively. Most frequent side effects observed were nausea, vomiting and alopecia. No significant differences regarding these or other side effects were obtained. Patients with stage IIB nonseminomatous testis tumor after retroperitoneal lymph node dissection are treated sufficiently with 2 courses of adjuvant cis-platinum-containing chemotherapy.

Risk/benefit of treating retroperitoneal teratoid bulky tumors.

Inductive polychemotherapy of germinal cell tumors in advanced stages (T0-4N3M0,1) is effective, yet accompanied by serious side effects. Partial remission necessitates resection of the residual tumor. The complications of the salvage operation are tolerable in proportion to its curativity. In a retrospective analysis, we evaluated the occurrence of toxic side effects and the frequency of intra- and postoperative complications in 128 patients with retroperitoneal teratoid bulky tumor. With a follow-up of three to one hundred ten months (means = 43 months), 91 patients (71%) are alive without evidence of disease; 28 patients (22%) died of apparent tumor progression.

Multiple nodular foci in the liver associated with chronic hepatic porphyria after previous treatment of breast cancer.

More than 7 years after the diagnosis and treatment of breast cancer (T1N1aM0), multiple nodular foci were observed in the liver of a 40-year-old woman at ultrasonographic examination. The lesions were confirmed by CT scan, but CT-guided liver biopsy revealed only non-specific alterations. At subsequent peritoneoscopic examination, bluish-brown foci were indeed visible on the liver surface, but guided liver biopsies again failed to corroborate the suspected metastases. Instead, histology showed mild portal fibrosis, moderate steatosis and siderosis of hepatocytes, as before. Only the intense red fluorescence of part of the biopsy material under Wood's light suggested the diagnosis of chronic hepatic porphyria or porphyria cutanea tarda, here presumably as a consequence of prolonged alcohol consumption. Subsequent porphyrin studies in urine, faeces and plasma yielded the typical constellation of latent porphyria cutanea tarda (chronic hepatic porphyria type C). The activity of erythrocyte uroporphyrinogen decarboxylase was normal, which argued against a genetic predisposition. After 1 year of strict alcohol abstinence and low-dose chloroquine treatment the "nodular foci" in the liver were no longer visible on ultrasonogram and CT scan; only proton-weighted NMR imaging (SE 1500/30) still showed ill-defined areas of higher signal intensity. The renal excretion of porphyrins had decreased considerably. The levels are now consistent with the diagnosis of subclinical chronic hepatic porphyria type A. Modern non-invasive imaging techniques are tremendously useful, but they have their pitfalls. Focal liver lesions may present serious diagnostic problems, especially when they are found in a patient with a history of carcinoma at an extrahepatic primary site. A rare example is described.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemotherapy of a patient because of spuriously elevated alpha-fetoprotein levels. Identification of the responsible factor.

Because of spuriously elevated alpha-fetoprotein levels, a course of polychemotherapy was given to a patient. We purified and identified the serum factor responsible for falsely high AFP levels as an IgG directed against mouse IgG. On gel filtration it behaves differently from true AFP, exhibiting a molecular weight of around 150,000. Chromatography on 'Protein A-Sepharose' revealed properties indistinguishable from those of IgG. The patient had never been treated with mouse antibodies, neither for diagnostic nor therapeutic purposes and he had had no contact with animals professionally.

[Risk and benefit of the treatment of bulky retroperitoneal teratoid tumors]. / Risiko und Nutzen der Behandlung retroperitonealer teratoider "Bulky"- Tumoren.

Inductive polychemotherapy of germinal cell tumors in advanced stages (T0-4N3,4M0,1) is effective, but is accompanied by serious side effects. If partial remission occurs, it is necessary to resect the residual tumor. The complications involved in this salvage operation are tolerable in relation to the prognosis. In a retrospective analysis, we evaluated the occurrence of toxic side effects and the frequency of intra- and postoperative complications in 128 patients with retroperitoneal teratoid bulky tumor. After a follow-up period of 3-110 months (mean = 43 months), 91 patients (71%) are still alive with no evidence of disease; 28 patients (22%) have died of apparent tumor progression.

[Multiple circular liver foci in latent porphyria cutanea tarda]. / Multiple Leberrundherde bei latenter Porphyria cutanea tarda.

A 41-year-old patient with latent porphyria cutanea tarda is described; 8 years after mastectomy for carcinoma, sonography and CT showed multiple hepatic foci, which were at first interpreted as liver metastases. A liver biopsy was carried out during laparoscopy and u/v fluorescence and subsequent laboratory tests confirmed the diagnosis of porphyria cutanea tarda. Treatment with resochin produced almost complete resolution of the liver abnormalities within 9 months. Magnetic resonance tomography using proton-weighted SE sequences showed a few foci of high signal intensity.

The pharmacokinetics of melphalan during intermittent therapy of multiple myeloma.

During intermittent melphalan-prednisone therapy the area under the plasma concentration-time curve of melphalan increased by an average of 45% after oral or intravenous administration of the drug in myeloma patients during the initial three courses at six-week intervals. The rise in melphalan plasma concentrations could not be referred to an alteration in melphalan elimination, metabolism, erythrocyte/plasma partition ratio, or protein binding. A possible explanation could be that covalent binding sites of melphalan were successively saturated during intermittent treatment, resulting in higher drug concentrations during successive courses of therapy.

[Therapeutic results in small-cell bronchial carcinoma after ACO II chemotherapy and adjuvant radiation]. / Therapieergebnisse des kleinzelligen Bronchialkarzinoms nach ACO II-Chemotherapie und adjuvanter Radiatio.

During the period from 1980 through 1984, 67 patients suffering from small-cell bronchial carcinomas were submitted to a complete ACO II treatment scheme combined with adjuvant irradiation. The complete remission rate was 12%, the partial remission rate 74%. Half of the patients with limited disease survived 12.3 months or more. The median survival time of patients with extensive disease was eight months. An irradiation of the tumor core had been found useful in cases where remote hematogenous metastases could not be demonstrated. It was shown that a prophylactic skull irradiation after the second chemotherapy series was applied too early, because persisting primary tumor residues formed late intracerebral metastases.

[Chemotherapy of dysgerminoma]. / Chemotherapie des Dysgerminoms.

Two patients with metastases after primary surgery to remove a dysgerminoma were successfully treated by chemotherapy. One received monotherapy with chlorambucil, the other vinblastine, bleomycin and cisplatin followed by irradiation. Both survived 5 years without evidence of disease. Dysgerminomas are highly sensitive not only to irradiation but also to chemotherapy. It is suggested that in younger women, in order to preserve fertility, chemotherapy should be used after primary conservative surgery, and irradiation only as a third-line remedy.

Adjuvant chemotherapy in nonseminomatous testicular tumour stage II.

Preliminary results of a random prospective trial to investigate the necessary extent of adjuvant chemotherapy are presented. Two hundred and sixty-three patients entered the study, of whom 210 (forty-eight stage IIA patients, 162 stage IIB patients) could be evaluated. Two hundred and eight patients are currently free of disease, since three of the five patients with relapses (one stage IIA patient, four stage IIB patients) achieved a complete remission. One IIB patient who had relapsed achieved a partial remission, whereas the final IIB patient who progressed is presently undergoing chemotherapy. One patient died of pneumonia after the first course of VBP. Toxicity consisted mainly of nausea, vomiting and loss of hair, 17% of the patients suffered infection, and 7% experienced sepsis.

Antimicrobial prophylaxis in immunocompromised patients.

The results of a randomised, prospective trial to investigate the efficacy of prophylactic treatment with ofloxacin during granulocytopenia after cytostatic treatment are presented. 42 patients with metastasised testicular germ-cell tumours entered the study. Cytostatic treatment consisted of at least 4 courses, 2 of which were succeeded by prophylactic treatment with ofloxacin. Three patients undergoing prophylactic treatment developed fever. Fever occurred in 16 patients during control phases (no ofloxacin prophylaxis) of cytostatic treatment. Seven of the 19 infections could be documented microbiologically. No side effects that related to ofloxacin were noted. In conclusion, ofloxacin was highly effective in the prevention of infection and, therefore, should be given prophylactically to patients with granulocytopenia.

[Epirubicin--results in breast cancer]. / Epirubicin--Ergebnisse beim Mammakarzinom.

Patients with metastasized breast cancer are incurable. Remissions with longer survival can be induced by chemotherapy in 50 to 80%, with 10 to 20% complete remissions, however, recurrence is unavoidable. Therefore the strategy of therapy in breast cancer must include two aspects: first prolongation of overall survival by multiple remissions with regimes that are not cross-resistant and secondly conservation of quality of life by minimization of therapy conditioned side-effects. Epirubicin, the new anthracycline derivate and analogue of doxorubicin (probably the most active chemotherapeutic agent against breast cancer) exhibits the same high activity but lower side-effects compared with the parent compound. Complete and partial remissions in 33% of 313 breast cancer patients could be achieved with epirubicin. In three other studies the efficacy and side-effects of epirubicin were compared with the established drug doxorubicin. The remission rate was nearly the same but the side-effects such as nausea, vomiting, stomatitis, bone marrow toxicity and congestive heart failure were lower. Five different studies with epirubicin in combination with other cytostatics have shown comparable results as adriamycin combinations. In a randomized multicenter study, 520 patients were treated with epirubicin or doxorubicin in combination with cyclophosphamide and fluorouracil. The remission rates were 52 vs. 54%, respectively, but the toxicity of the epirubicin combination group was significantly lower.