Intraarterial Chemotherapy for Brain Tumors: A Summary of the Ottawa Experience

Stewart, D. J.

doi:10.1007/978-94-009-3347-7_72

Cited by 2 publications

(2 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has previously been reported that intracarotid etoposide will transiently disrupt the blood-brain barrier in normal brain [10]. Against this explanation is the fact that intensity of brain tumor enhancement has generally not increased substantially following our intracarotid regimens [11]. In support of this explanation is the fact that 2 of the 3 patients classified as having stable disease on the phase II study (including the patient with neurological improvement) were among the 4 patients who received prior intracarotid chemotherapy.…”

Section: Discussionsupporting

confidence: 63%

Phase II study of weekly intravenous menogaril in the treatment of recurrent astrocytomas in adults

et al. 1992

View full text Add to dashboard Cite

Twenty patients with astrocytomas recurrent after surgery +/- radiation were treated on a phase II protocol of the new anthracycline derivative menogaril 115 mg/m2 administered intravenously once per week. Sixteen patients were evaluable for treatment efficacy. No patient achieved a major therapeutic response. Three patients (19%) had stable disease for greater than 8 weeks, including one who showed minor evidence of tumor regression, but less than 50%. Thirteen patients failed. Treatment was well tolerated. One patient developed granulocytopenia, while none developed thrombocytopenia. Four patients required an interruption in their treatment for one to two weeks because of development of granulocytopenia (one patient) or other reasons. Other toxic effects included arm vein phlebitis and skin irritation, skin discoloration of the infused arm, mild to moderate nausea and vomiting, diarrhea, stomatitis, and a fatal central venous catheter infection. Despite the fact that menogaril appeared to have therapeutic activity against recurrent astrocytomas in our phase I studies, we could not document any activity in this phase II study.

show abstract

Section: Discussionsupporting

confidence: 63%

Phase II study of weekly intravenous menogaril in the treatment of recurrent astrocytomas in adults

et al. 1992

View full text Add to dashboard Cite

show abstract

“…Tumour cell resistance is probably a far more important reason for chemotherapy failure than is inability of the drug to cross the intact BBB, and any barrier might make relatively little difference for a highly cytotoxic drug (Wodinsky et al, 1977). Hence both we (reviewed in Stewart et al, 1983, 1986a-c, 1987a, 1989a, 1990a,b, 1994ac, Feun et al, 1985Stewart, 1987aStewart, ,b, 1989Stewart, , 1994 and several other investigators (reviewed in Kolaric et al, 1981;Rosner et al, 1983;Kantarajian et al, 1984;Stewart, 1989) (Shapiro, 1983). For lipid-insoluble drugs, cell membrane factors may be more important determinants of drug entry than is blood flow (Dedrick et al, 1975).…”

Section: D6cussionmentioning

confidence: 71%

Factors affecting platinum concentrations in human surgical tumour specimens after cisplatin

Molepo²,

Rm³

et al. 1995

Br J Cancer

View full text Add to dashboard Cite

SinaryWe asessed factors which affect cisplatin concentrations in human surgical tumour specmen. al., 1994a;Stewart, 1994). For many chemotherapy drugs, only low concentrations are found in normal brain and cerebrospinal fluid (CSF), because of the BBB and blood-CSF barrier, but the barrier is often largely disrupted in patients with brain tumours (Blasberg and Groothuis, 1986). In animal models, the degree of BBB disruption varies from one type of tumour to another and between parts of the same tumour (Groothuis et al., 1981;Blasberg and Groothuis, 1986). Lower concentrations of chemotherapy drugs (Levin et al., 1972;Tator, 1976;Groothuis et al., 1981) and lower capillary permeability (Hasegawa et al., 1983) It has also been argued that resistance of IC tumours may be due in part to invasion of tumour cells into the brain adjacent to tumour (BAT), where the BBB is more intact, and where drug concentrations are lower than in the main body of the tumour (Levin et al., 1975). However, the importance in brain tumour chemotherapy of resistance of tumour cells in the BAT remains controversial. Since even small numbers of tumour cells may induce leakiness in local blood vessels (Stewart et al., 1987), small tumour deposits in the BAT could result in a very localised increase in drug concentrations, and it is uncertain how drug concentrations compare in individual tumour cells in BAT vs the main tumour body.We have studied several chemotherapy drugs with respect to the concentrations reached in human IC tumours (reviewed in Stewart et al., 1994a, Stewart, 1994. Concentrations in IC tumours appeared to be similar to those in EC tumours for cisplatin, phosphonacetyl-L-aspartate, 4'-(9-acridinylamino)-methanesulphon-m-aniside (AMSA), pentamethylmeamine, doxorubicin and vinblasine. Concentrations of etoposide and mitoxantrone in IC tumours were somewhat lower than in EC tumours. Since no EC tumour samples were available, comparisons were not possible for a variety of other agents, but for most of these drugs potentially cytotoxic concentrations were achieved in human IC tumours. Low drug concentrations in normal brain and CSF did not preclude high concentrations in IC tumours.In this paper, we report the results of further studies of human tumour accumulation of the chemotherapy drug cisplatin. These studies were done since our earliest studies of surgical specimens had looked only at IC tumours. While our later autopsy studies had looked at both IC and EC tumours, there were differences between patients with respect to drug doses, time from last treatment to death, concurrent drugs, etc. (reviewed in Stewart et al., 1994a; Stewart, 1994). Hence, we conducted the studies reported in this paper so that a companson could be made between IC and EC tumours

show abstract

Intraarterial Chemotherapy for Brain Tumors: A Summary of the Ottawa Experience

Cited by 2 publications

References 18 publications

Phase II study of weekly intravenous menogaril in the treatment of recurrent astrocytomas in adults

Phase II study of weekly intravenous menogaril in the treatment of recurrent astrocytomas in adults

Factors affecting platinum concentrations in human surgical tumour specimens after cisplatin

Contact Info

Product

Resources

About