Thema: Welche Möglichkeiten noch bei Astrozytom III

Hallo!
Meine 20 jährige Schwester hat am 02. Dezember 2002 die Diagnose inoperabels, anaplastisches Astrozytom III, bekommen!
Seither hatt sie schon Bestrahlungen und mehrere Chemotherapien!
Anfänglich war es "nur" eine linksseitige Lähmung des Armes, der Hand, des Beines und des Fusses! Mittlerweile beginnt eine zunehmende Kraftlosigkeit des rechten Beines und eine je nach Tagesform heftigere oder leichtere Spastik! (Linkes Bein - Streckspastik; Linker Arm - Beugespastik; jetzt teilweise Beginn des rechten Beines mit der Streckspastik!)
Im Moment bekommt sie eine orale Chemo und wir gehen mit ihr 2x / Woche zur Hyperthermie - Bestrahlung!
Wir hoffen natürlich, dass diese Behandlung was bingt, sind aber nach wie vor verzweifelt auf der Suche nach Leutem die auch andere Behandlungs-
möglichkeiten kennen oder Erfahrungen mit anderen Sachen gemacht haben, evtl. Misteltherapie, mögliche Operationen, erfahrenen Zentren für Hirntumore, evtl. fähigen und zuverlässigen Ärzten in unserem Unkreis (Neustadt a.d. Aisch), Leuten die evtl. bereits Erfahrungen gemacht haben mit der Hyperthermie,... !
Falls jemand etwas weiß, wir freuen uns über alle Zuschriften und Meinungen!!
Ansonsten wünsche ich allen Betroffenen und ihren Angehörigen weiterhin sehr viel Kraft und Mut und hoffe mit Euch, dass alles gut ausgehen wird!
LG Christine!

Christine,

welche hat sie bekommen?
welche Chemo bekommt sie momentan,
(Nenne bitte die medizinischen Begriffe).

Gruß Will

Hallo Willi!

Meine Schwester hat bisher drei Chemotherapien intravenös bekommen, allerdings muss ich erst nachschauen wie sie hies!
Die jetzige Chemo ist eine oral verabreichte Chemo mit Temozolomid 100mg. Sie muss 5x / Woche, jeden Tag eine Stunde vor dem Frühstück eine Tablette nehmen. Insgesamt ist die Chemo auf acht Wochen angesetzt (zwei Wochen hat sie sie schon genommen und diese ist die dritte!)
Weiterhin nimmt sie noch Tegretal 200mg (1 - 0 - 1); Pantozol 40mg (0 - 0 - 1) und Decortin 20mg (1/4 - 0 - 1/4)!
Antidepressiva nimmt sie im Moment noch keine, wobei wir den Arzt drum bitten werden, da sie seit der Rückkehr von ihrer Frühreha (und dort auch schon, weil es ihr dort überhaupt nicht gefallen hat und auch die Schwestern usw. sehr gleichgültig waren), d.h. jetzt schon ein paar Wochen sehr starke Stimmungsschwankungen hat.
Ich hoffe ich hab nix an Information vergessen und freu mich schon auf eventuelle Antworten!

Gruß Christine

Hallo Christine,

wer hat den die Inoperabilität des Tumors festgestellt, oft kann man eben
doch noch Astro III operieren, aber es gibt eben nur wenige Neurochirurgen, die das können.

Eine gute Adresse ist hier sicher Herr Prof. Dr. Siegfried Vogel, Neurochirurg
am St. Gertrauden Krankenhaus in Berlin (Tel. 030 - 8272 - 2180) Vielleicht macht es einen Sinn, die aktuellen MRT Bilder zu ihm zu senden. Wir kennen einige Astro II und III Fälle, in denen Prof. Vogel erfolgreich operiert hat, obwohl andere Ärzte bereits aufgegeben hatten.

Gruss und viel Kraft
Reiner

Christine,

unten ein paar Abstracts zu noch nicht fest etablierten Verfahren.
mit der Datenbank unter http://www.ncbi.nlm.nih.gov/entrez/query.fcgi
kann man diese Abstracts auch selber finden
z.B. eingeben tamoxifen glioma oder tamoxifen polythiouracil.

Es sieht so aus, dass auch die derzeitige Chemo nicht viel bringt.
Was bleibt dann noch? Eigentlich nur, dass man die ausgetretenen Pfade verläßt, sich in der Literatur umschaut, und hofft, dass man etwas findet, was möglicherweise helfen könnte.

Unten habe ich eine Reihe Abstracts aufgeführt, die eine Chance bieten, dass die Krankheit noch aufgehalten wird.

z. B. alfahydroxycholcalciferol, ein Vitamin-D-Derivat, oder
Phenylbutyrat, beides Praeparate, die zur Differenzierung von Tumorzellen eingesetzt werden. Hohe Differenzierung bedeutet "Gutartigkeit".
s. Abstracts. Mit beiden Substanzen werden Erfolge gemeldet.


Oder HD-Tamoxifen unter Zusatz von Propythiuracil, letzteres wird zugesetzt, um eine Schilddrüsen-Unterfunktion und damit eine IGF-1 Reduzierung, zu erzeugen.
Das schafft man damit vielleicht bei der Hälfte der Fälle.
Wenn es glingt, ist Wahrscheinlichkeit hoch, dass Tamoxifen (wenigstens eine Zeitlang hilft). Es gibt Leute, die glauben, dies Prinzip verallgemeinern zu können, und setzen Präparate, die die Funktion der Schilddrüse herabsetzen, auch anderen Chemotherapeutika zu.

PCV plus DFMO wäre die beste derzeit verfügbare Chemotherapie für Grad III Tumore. Da Deine Schwester aber vorbehandelt ist, weiß ich nicht. ob es Sinn macht, jetzt mit PCV anzufangen. Die Autoren meinen in der Studie aber, es könne Sinn machen,
DFMO (Di fluoro methyl ornithin) auch allein zu nehmen.

An eine Strategie würde ich in der Sitution ganz sicher auch denken,
in München wird mit radioaktiv markierten Antiköpern experimentiert.
(s. Abstract). Vielleicht ist man dort bereit, das Verfahren bei Deiner Schwester einzusetzen.

In Berlin git es den Neurochirugen Prof. Vogel, der immer noch eine Idee hat, wenn andere keine mehr haben. In Dülmen, (Franz-Hospital) im nördlichen Ruhrgebiet den Dr. Dresemann, der ebenfalls in Notfällen experimentierfreudig ist (s. Abstract)

Auch mit rezeptfreien Präparaten kann man etwas machen, z.B. mit Laif 600 aus der Apotheke. Da müßte man aber 12 Tabletten pro Tag nehmen.

Wenn aufgrund des Wirkstoffs Hypericin Sonnenlichtempfindlichkeit auftritt, ist dies ein Zeichen, dass man in der richtigen Dosierung ist.
Auch zu Hypericin könnte ich ein Abstract bingen, allerdings nur zu einer invitro-Studie. Ich kenne aber Leute, die machten eine Zeitlang sagenhafte Fortschritte in geradezu hoffnungsloser Situation, als sie synthetisches Hypericin nahmen, u.a. meine Frau. Allerdings hielt die Besserung nur ein halbes Jahr an.

Ich könnte noch weitere Substanzen anführen, die man mehr oder weniger chronisch schluckt, die etwas können, die aber nicht die Blutwerte zu sehr verschlechtern z.B. Hoch-Dosis Roaccutane (ein Mittel) gegen Akne, in der Literatur zu finden unter 13-cis-retinoic acid (im Abstract eingesetzt zusammen mit Temozolomid). Es kann aber auch allein etwas, wie eine Studie aus jahre 1996 zeigt (Abstract)

Man sieht, es gibt mehr Möglichkeiten als man denkt. Aber keine bringt den sicheren Erfolg. Wenn man keinen Erfolg hat, dann ist es gut, die nächste Therapie schon vorgedacht zu haben, sonst läuft einem die Zeit weg.

Gruß Willi






Anticancer Res. 2003 Jan-Feb;23(1B):617-26.
Propylthiouracil-induced chemical hypothyroidism with high-dose tamoxifen prolongs survival in recurrent high grade glioma: a phase I/II study.
Hercbergs AA, Goyal LK, Suh JH, Lee S, Reddy CA, Cohen BH, Stevens GH, Reddy SK, Peereboom DM, Elson PJ, Gupta MK, Barnett GH.
Department of Radiation Oncology, Cleveland Clinic Foundation, 9500 Euclid Ave, S80, Cleveland, OH 44195, USA.
BACKGROUND: High-dose tamoxifen has had disappointing results as a palliative therapy in recurrent glioma. Insulin-like growth factor 1 (IGF-1) is a thyroid hormone modulated naturally occurring antagonist of tamoxifen-induced cytotoxicity. Thyroid function was suppressed to reduce IGF-1 levels in glioma patients and high-dose tamoxifen administered. MATERIALS AND METHODS: Propylthiouracil was used to induce chemical hypothyroidism in 22 patients with recurrent glioma. Tamoxifen was started within one month and given in escalating doses from 40 mg twice a day up to 80 mg 3 times a day. No significant toxicity developed. RESULTS: Eleven out of 22 patients became hypothyroid. No patients experienced symptoms of clinical hypothyroidism. Median survival was significantly longer in the hypothyroid group (10.1 months versus 3.1 months); p = 0.03. There was a significant decrease in blood levels of IGF-1 (p = 0.02). in hypothyroid patients. CONCLUSION: Patients treated for recurrent high-grade gliomas with high-dose tamoxifen had significantly longer survival when chemical hypothyroidism was induced with propylthiouracil.



Cancer. 2003 May 1;97(9 Suppl):2363-73.
Combination therapy with irinotecan and protein kinase C inhibitors in malignant glioma. Chen TC, Su S, Fry D, Liebes L.
Department of Neurosurgery, University of Southern California, School of Medicine, Los Angeles, California 90033, USA. tcchen@hsc.usc.edu
The topoisomerase-I inhibitor irinotecan (CPT-11) is currently used in Phase I/II trials for the treatment of patients with recurrent malignant gliomas. Protein kinase C (PKC) inhibitors such as high-dose tamoxifen and hypericin also have been used in the treatment of malignant gliomas. The current study examined the role of PKC inhibitors as chemosensitizers for CPT-11 and their proposed mechanism of action. Two glioma cell lines (A-172 and U-87) and one primary glioma cell culture (LA-567) were used. Proliferation ((3)H-thymidine) and cytotoxicity (methylthiotetrazole) studies were performed using CPT-11 (0-100 microM) alone, 7-ethyl-10-hydroxy camptothecin (SN-38) (0-1000 nM) alone or in the presence of a PKC inhibitor, tamoxifen (10 microM), hypericin (10 microM), calphositin C (400 nM), or staurosporine (10 nM). The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) assay was used to determine apoptosis as the mechanism of cytotoxicity; alterations in bcl-2 and bax expression were determined using Western blot analysis. Conversion of CPT-11 to SN-38 by glioma cells was determined using high-performance liquid chromatography (HPLC) analysis. Increasing CPT-11 and SN-38 concentrations induced cytotoxic morphologic changes, decreased proliferation, and increased cytotoxicity on all glioma cell lines tested. These changes were increased in the presence of a PKC inhibitor. The mechanism of the cytotoxicity was determined to be apoptosis by the TUNEL assay. The combination of a PKC inhibitor with CPT-11 or SN-38 led to decreased expression of the antiapoptotic protein bcl-2, and increased expression of the proapoptotic protein bax. HPLC analysis demonstrated conversion of CPT-11 to SN-38 by glioma cells. A combination of CPT-11 or SN-38 with a PKC inhibitor was found to lead to a decrease in proliferation and an increase in apoptosis in malignant glioma cells. The induction of apoptosis was secondary to a decrease in bcl-2 and an increase in bax expression. Glioma cells are capable of converting CPT-11 to SN-38 by intrinsic tumor carboxylesterases. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11307


J Neurooncol. 2002 Sep;59(3):239-42.
Complete response of a recurrent, multicentric malignant glioma in a patient treated with phenylbutyrate. Baker MJ, Brem S, Daniels S, Sherman B, Phuphanich S. Neuro-Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612-9497, USA. Sodium phenylbutyrate is a biological-response modifier that acts as a dose-dependent inhibitor of glioma cell proliferation, migration, and invasiveness in vitro, possibly by inhibition of urokinase and c-myc pathways. Despite its biological activity in vitro, there have not been any prior reports of efficacy in the treatment of human malignant gliomas. We report a 44-year-old female with a recurrent, multicentric, malignant glioma who experienced a durable remission lasting more than four years. The patient initially presented with seizures caused by a biopsy-proven anaplastic astrocytoma of the frontal lobe. The patient was treated with radiation therapy and Procarbazine-CCNU-Vincristine (PCV). However, the tumor progressed and extended to the corpus callosum with midline shift, refractory to four cycles of continuous 72-h infusion of BCNU/Cisplatinum. Additional enhancing lesions appeared in the left frontal and left temporal lobes. The patient was started on sodium phenylbutyrate, 18 g daily in three divided oral doses, and reduced to 9 g/day and eventually to 4.5 g/day to eliminate mild, reversible side effects. Four years later, the patient has a KPS functional score of 100%. Phenylbutyrate is a well-tolerated, oral agent that shows potential for the treatment of malignant gliomas. Further studies should be considered to identify a subset of patients that have tumors sensitive to phenylbutyrate, either as a single agent or in combination with radiation therapy or other chemotherapeutic agents.


Clin Cancer Res. 2003 Mar;9(3):981-90.
Phase III Randomized Study of Postradiotherapy Chemotherapy with Combination alpha-Difluoromethylornithine-PCV versus PCV for Anaplastic Gliomas. Levin VA, Hess KR, Choucair A, Flynn PJ, Jaeckle KA, Kyritsis AP, Yung WK, Prados MD, Bruner JM, Ictech S, Gleason MJ, Kim HW.
Departments of Neuro-Oncology [V. A. L., K. A. J., A. P. K., W. K. A. Y., S. I., M. J. G.], Pathology, Section of Neuropathology [J. M. B.], and Biostatistics [K. R. H., H-W. K.], M. D. Anderson Cancer Center, Houston, Texas 77030-4009. PURPOSE: In the current study, we sought to determine whether the addition of DFMO (alpha-difluoromethyl ornithine; eflornithine), an inhibitor of ornithine decarboxylase, to a nitrosourea-based therapy procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, vincristine (PCV) would be more effective as a postirradiation adjuvant therapy for anaplastic gliomas (AG) than PCV alone. PATIENTS AND METHODS: After conventional radiation therapy, 249 AG patients were randomized to receive either DFMO-PCV (125 patients) or PCV alone (124 patients), with survival being the primary endpoint and progression-free survival being an important secondary endpoint. The starting dosage of DFMO was 3 grams/m(2) p.o. q. 8 h for 14 days before and 4 weeks after 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea; PCV was administered as described previously (1). Clinical and radiological (gadolinium-enhanced magnetic resonance imaging) follow-ups were nominally at the end of each 6- or 8-week cycle (PCV at 6 weeks; DFMO-PCV at 8 weeks). Laboratory evaluations for hematological and other adverse effects were at 2-week intervals. RESULTS: In the DFMO-PCV arm, there were 114 evaluable patients with 78.1% anaplastic astrocytoma (AA), 3.5% anaplastic oligoastrocytoma (AOA), 14% anaplastic oligodendroglioma (AO), and 4.4% other malignant gliomas. These histological groupings were comparable with those of the 114 patients in the PCV arm: (a) 69.3% AA; (b) 7% AOA; (c) 21.1% AO; and (d) 2.6% malignant gliomas. Although improved survival estimates for the DFMO-PCV treatment group persisted over the course of the study, analysis of survival differences over the entire follow-up period did not yield significance (P = 0.11). However, careful analysis of the corresponding hazard and hazard ratio functions indicated that the real treatment difference was limited to the first 24 months of follow-up (P = 0.02). The median progression-free survival for the two treatment groups, as measured from postradiotherapy registration, was 71.1 months for the DFMO-PCV arm and 37.5 months for the PCV-only arm. Median survival, measured from registration, was 75.8 and 61.1 months, respectively, for the DFMO-PCV and PCV arms. The treatment effect persisted when the AA histology was separated from AO and AOA histologies. This effect persisted even after adjusting for the covariates of age, Karnofsky performance status, and extent of surgery. There was a statistically significant increase in grade 3 adverse events for diarrhea and anemia associated with DFMO-PCV. Grade 3 or 4 adverse events of nausea, ototoxicity, and thrombocytopenia were not significantly increased among groups. CONCLUSIONS: The addition of DFMO to the nitrosourea-based PCV regimen in this Phase III study demonstrated a sustained benefit in survival probabilities for AG patients but not in the corresponding hazard rates. Survival analysis from registration found a DFMO-PCV median survival of 6.3 years (49 of 114 events), whereas that for PCV alone was 5.1 years (55 of 114 events). The hazard function demonstrated a difference over the first 2 years of study (hazard ratio 0.53, P = 0.02) but not after 2 years (hazard ratio 1.06, P = 0.84), supporting the conclusion that DFMO adds to the survival advantage of PCV chemotherapy for AG patients by direct temporal interaction with PCV.



Neurooncol. 2003 May;62(3):321-8.
Locoregional radioimmunotherapy in selected patients with malignant glioma: experiences, side effects and survival times.
Goetz C, Riva P, Poepperl G, Gildehaus FJ, Hischa A, Tatsch K, Reulen HJ.
Neurochirurgische Klinik der Ludwig-Maximilians-Universitat, Munchen, Germany. cgoetz@nc.med.uni-muenchen.de
Prognosis of malignant glioma is very unfavourable mainly due to minimal tumour remnants in the peritumoural tissue. Intralesionally applied radioimmunotherapy is a possible therapeutical option with the potential to improve survival of patients with malignant glioma. We investigated side effects and survival after surgery, conventional radiotherapy and additional radioimmunotherapy with labelled tenascin-antibodies in patients with malignant glioma. METHODS: Since 1995, 37 patients were treated with radioimmunotherapy after resection and radiotherapy of a malignant glioma. Patients received antibodies labelled with yttrium-90 and iodine-131 in different doses into the tumour cavity via a previously implanted ommaya-reservoir. Treatment was applied in up to 8 cycles (mean 2.96 cycles) in time intervals of 6-8 weeks. Mean age was 46 years, histology was anaplastic astrocytoma in 13 patients and glioblastoma in 24 patients. RESULTS: For the whole group median survival time has not yet been reached. For glioblastoma the median survival time is 17 months, 5-year survival probability for anaplastic astrocytoma is 85% approximately. Quality of life was acceptable. Acute side effects following treatment were headache, seizures and worsening of pre-existing neurological symptoms. Late side effects were skin necrosis and, in 1 case, a delayed aphasia probably due to a vascular lesion. CONCLUSION: Radioimmunotherapy prolonged survival time in a selected group of patients with malignant gliomas as compared to a historical control group. Patients with anaplastic astrocytomas seem to have more benefit from this therapy than patients with glioblastomas.


STI 571/hydroxyurea in progressive, pretreated glioblastoma (GB) patients (pts.) Year: 2003 Printable Version Abstract No: 465 Category: CNS Tumors Author: G. Dresemann; Franz-Hospital Duelmen, Duelmen, Germany, Abstract: Many malignancies of the brain including GB express epithelial growth factor-receptors (EGF-R) and platelet derived growth factor-receptors (PDGF-R). STI 571 is a signal transduction inhibitor for PDGF-R and c-kit with efficacy in chronic myeloic leukaemia and gastrointestinal stroma tumours (GIST). In GB, however, no significant efficacy could be seen as a single agent treatment due to missing penetration into the liquor. GB pts. with tumour progression after irradiation therapy and chemotherapy containing ACNU and temozolomid in one or more cytostatic schedules show rather poor prognosis. Efficacy of STI 571 was analysed in a group of 14 GB pts. with progressive disease (PD) after irradiation therapy and cytostatic treatment containing ACNU and temozolomid by clinical examination and magnetic resonance imaging (MRI) every 6 weeks. ECOG-performance status was 1 or 2. All pts. were treated with STI 571 400 mg p. o. /day combined with hydroxyurea 1000 mg p. o./day continuously. Combination with hydroxyurea, a well liquor penetrating drug, was chosen in order to assist STI 571 entering metabolism of the brain. No hydroxyurea related anti tumour effect could be expected in case of ACNU/temozolomid resistance. After a median treatment period of 27 weeks (4 to 71) stable disease (SD) over a period of at least 3 months was seen in 4 pts., partial response (PR) in 4 pts., complete response (CR) in 1 pt. and primary PD in 5 pts., no grade 3 or 4 toxicity occurred. One pt. with PR and 1 pt. with SD died due to embolism of the lung, 3 pts. died due to primary PD and 3 pts. died due to secondary PD. One pt. with PR could improve PS from 2 to 1, in 7 pts. PS remained unchanged. C-kit expression could be analysed in 6 pts., there was no correlation with response. In summary combination therapy with STI 571 and hydroxyurea was well tolerated and effective in this small group of progressive, pretreated GB pts., however, present observation time was short. Even in some pts. with PD tumour progression was unexpected moderate and long lasting under continued treatment, 4 pts. survived for at least one year. If these data can be confirmed, this treatment strategy should be examined in earlier stages of GB.


J Clin Oncol. 2003 Jun 15;21(12):2305-11.
Phase II evaluation of temozolomide and 13-cis-retinoic acid for the treatment of recurrent and progressive malignant glioma: a North American Brain Tumor Consortium study. Jaeckle KA, Hess KR, Yung WK, Greenberg H, Fine H, Schiff D, Pollack IF, Kuhn J, Fink K, Mehta M, Cloughesy T, Nicholas MK, Chang S, Prados M; North American Brain Tumor Consortium. University of Texas M. D. Anderson Cancer Center, Houston, USA. jaeckle.kurt@mayo.edu.
PURPOSE: Temozolomide (TMZ) and 13-cis-retinoic acid (cRA) have shown activity in prior single-agent trials of recurrent malignant gliomas (MG). This phase II trial evaluated efficacy and toxicity of combination temozolomide and cRA treatment in recurrent MG. PATIENTS AND METHODS: Adults with recurrent supratentorial MG for whom surgery, radiation, and/or chemotherapy failed were eligible. Treatment included oral TMZ 150 or 200 mg/m2/d, days 1 through 5, and cRA 100 mg/m2/d, days 1 to 21, every 28 days. Primary end point was progression-free survival at 6 months (PFS 6); secondary end points included response, survival, and PFS12. RESULTS: Eighty-eight eligible patients (glioblastoma multiforme [n = 40]; anaplastic gliomas [n = 48; astrocytoma, 28; oligodendroglioma, 14; mixed glioma, six]) received treatment. PFS 6 was 43% (95% confidence interval [CI], 33% to 54%) and PFS12 was 16% (95% CI, 10% to 26%). Median overall PFS was 19 weeks (95% CI, 16 to 27 weeks), and median overall survival (OS) was 47 weeks (95% CI, 36 to 58 weeks). OS was 46% (95% CI, 36% to 57%) at 52 weeks and 21% (95% CI, 13% to 31%) at 104 weeks. Of 84 assessable patients, there were two (3%) complete responses and eight (12%) partial responses (complete plus partial response, 15%). Among 499 treatment cycles, the most common grade 3/4 events included granulocytopenia (1.8%), thrombocytopenia (1.4%), and hypertriglyceridemia (1.2%). CONCLUSION: TMZ and cRA were active, exceeding our 20% thresholds for PFS 6 success, assuming 20% improvement over our previously reported database (glioblastoma multiforme: expected, 30%; observed, 32%; anaplastic glioma: expected, 40%; observed, 50%).


Clin Cancer Res. 1996 Dec;2(12):1931-5.
Treatment of recurrent malignant gliomas with high-dose 13-cis-retinoic acid.
Yung WK, Kyritsis AP, Gleason MJ, Levin VA. Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.

Malignant gliomas account for more than 60% of all primary brain tumors in adults. Adjuvant chemotherapy in addition to radical surgery and radiation therapy has provided only a modest increase in survival. Retinoic acid has been shown to have growth-inhibitory activity against glioma cells in culture. This provides the rationale for a Phase II study using 13-cis-retinoic acid (CRA) in patients with recurrent malignant brain tumors. The objective of this study was to determine the clinical activity of CRA in patients with a histologically proven diagnosis of malignant brain tumor and documented progressive or recurrent disease after radiation and chemotherapy. Fifty patients with documented recurrent disease were treated with CRA as a single agent p.o. at a dose of 60-100 mg/m2 per day. Three weeks of treatment were followed by 1 week of rest. Of the 43 patients who received more than 4 weeks of therapy, 3 (7%) achieved partial response, 7 (16%) achieved minor response, 13 (30%) remained stable, and 20 (47%) had disease progression. The median time from onset of treatment to disease progression for the whole group of 43 patients was 16 weeks (19 weeks for glioblastomas and 11 weeks for anaplastic glioma), whereas that for the 23 patients with partial response and minor response and who remained stable was 66 weeks, and that for the 20 patients with progressive disease was only 8 weeks. The median survival time for glioblastoma was 58 weeks, and 34 weeks for anaplastic astrocytoma. Toxicity was mainly dermatological, with dry skin and cheilitis. These preliminary results suggest that 13-cis-retinoic acid is active against malignant gliomas and is very well tolerated.