Intralesional Mistletoe Injections into Hepatic Metastases in Colorectal Carcinoma and into the Primary Hepatocellular Carcinoma (HCC).

(Translation of Intralläsionale Mistelinjektionen in Lebermetastasen bei kolorektalem Karzinom und in das primäre Hepatozelluläre Karzinom (HCC))
Special Print of Der Merkurstab, 06/1997, p. 41

H. Matthes
Gemeinschaftskrankenhaus Havelöhe, Berlin

Abstract:

Introduction

Colorectal carcinomas often lead to hepatic metastases. A satisfactory treatment of solitary and multiple metastases does not exist. Surgical segmental resection. chemoembolization or chemotherapy (e.g. with 5-FU, cisplatinum etc.) are still unsatisfactory or not always possible. The same applies to HCC.

Study design

In 21 patients with hepatic metastases of a colorectal carcinoma and 6 patients with HCC, mistletoe extract (Helixor MR) was administered intralesionally (sonographically controlled puncture) in increasing doses (100 - 2500 mg) 1 - 3 times a week. The target criterion in the hepatic metastases in colorectal.carcinoma were the metastasis size durin2 the course under intralesiona.1 injection treatment and the tumour markers CEA and CA19-9 in the serum, in HCC the size of the tumour and the alphafetoprotein (AFP) in the serum.

Results

Of the 21 patients with hepatic metastization in colorectal carcinoma, metastasis reduction occurred in 11 patients under intralesional Helixor injection (52%: 1 patient displayed a reduction in the metastasis size > 75%; 4 patients > 50% and 6 > 25% of the initial diameter of the metastasis). On average at least 7 injections were needed and the dose administered in each injection was based on the increasing,-dose method (in steps of 100 mg; 300 mg; 500 mg; 1000 mg; 1500 mg.; 2500 mg. Helixor M) usually with 1000 mg to 1500 mg per administration. In 3 patients systemic side-effects such as flush, wealing of the skin, diarrhoea, nausea, retching occurred during the course of the intralesional injections. In no case was administration of steroids necessary, and once an HI-antagonist was administered. All 11 cases which responded and in which the tumour markers CEA and CA19-9 were raised displayed a reduction in serum concentration.

In the 6 cases of HCC, one of which was a multifocal fibrolamellar HCC, 5 out of the 6 cases displayed a reduction in the diameter of the HCC (2 patients > 75%, 2 patients > 50% and one patient > 25% reduction from the initial diameter of the HCC). Only the multifocal fibrolamellar HCC displayed no significant reduction in diameter. Since this had increased, however, in diameter from 26 mm to 51 = in 14 days, the inhibition of progression alone must be regarded as a success (under intralesional administration every other day no further growth progression). The AFP level was significantly reduced in all 5 cases of HCC under mistletoe treatment (p < 0.025). In the case of the AFP-negative fibrolamellar HCC this parameter was not recordable.

Discussion

High-dose intralesional administration of mistletoe extract in hepatic metastases of colorectal carcinoma appears to be a treatment option with a response rate of 50%. This treatment option must, however, be clinically indicated since no data are available as yet which signalize increased survival in addition to a reduction in metastasis size. This requires additional controlled studies.

Hi.h-dose intralesional administration of mistletoe extract appears to be a good treatment option (in non-fibrolamellar) HCC. All non-fibrolamellar HCCs displayed repressive growth after injection of mistletoe.

As studies with alcohol injections in reduction of the HCC also display increased survival, it is to be expected that this good response of the mistletoe injection in HCC also leads to increased survival. This can also be supposed on the basis of the clinical development of the patients in the study since survival times of over 24 months were achieved with initial HCC sizes of > 12 cm.