CT-guided intratumoural administration of cisplatin/epinephrine gel for treatment of malignant liver tumours

T J Vogl, K Engelmann, M G Mack, R Straub, S Zangos, K Eichler, K Hochmuth, E Orenberg, T J Vogl, K Engelmann, M G Mack, R Straub, S Zangos, K Eichler, K Hochmuth, E Orenberg

Abstract

To analyze prospectively the interventional and clinical aspects of computed tomography-guided direct intratumoural injection of a novel chemotherapeutic administration and the parenchymal changes of tumour and necrosis in malignant liver tumours. Eight patients with 17 colorectal liver metastases were treated with a mean of 5.1 injections and nine patients with 13 hepatocellular carcinoma nodules with a mean of 3.1 treatments with computed tomography guided local applications of a novel cisplatin/epinephrine gel. This application provides a higher local and lower systemic drug concentration. Volumes of tumour and necrosis prior and after treatment were measured by computer generated volumetric analysis. Contrast enhanced studies verified pretherapeutic viable tumour volumes with a value of 77.4 ml in the metastases and 29.2 ml in the hepatocellular carcinoma nodules. Intratumoural drug application resulted in a significant increase of necrosis and a decrease in viable tumour volume to be 68.3 ml in metastases and 14.5 ml in hepatocellular carcinoma. Local therapy control rate for the follow up to 6 months was 38 and 71% for the group of metastases and hepatocellular carcinoma, respectively. Direct intratumoural injection of cisplatin/epinephrine injectable gel is a feasible and good tolerated method and results in the development of a statistically significant increase in necrosis in malignant liver tumours. For hepatocellular carcinoma a higher local therapy control rate compared to colorectal metastases can be reported.

Figures

Figure 1
Figure 1
Visualization of the injection procedure in a hepatic metastasis (open arrows) shown in segment 5 using the CARE vision CT programme. Note the needle placed centrally in the tumour (arrow).
Figure 2
Figure 2
Volumetric measurements of viable tumour volumes before treatment (screen) and 2 weeks and 2 months after last treatment.
Figure 3
Figure 3
(a) 69-year-old patient with histopathologically proven HCC in segment 5/8. Pretreatment CT scan on the left side, lesion identified with decreased attenuation values. CT scan 2 weeks after the fourth/last treatment with IntraDose® gel. Segment 5/8 reveals an irregular area of necrosis that developed after treatment (arrows). Both scans portal venous phase. (b) MRI scan (T2-weighted) 2 years after treatment, The lesion is still detectable but has not changed in size, the patient is in a good clinical condition.
Figure 4
Figure 4
A 55-year-old patient with colorectal metastases to the liver. (a) Pretreatment CT scan in segment 8 (portal venous phase). (b) CT scan (portal venous phase) at 8 weeks after the pretreatment evaluation and 2 weeks after the fourth treatment. Increased tumour necrosis is evident after treatment.

References

    1. AugustDASugarbakerPHOttowRT1985Hepatic resection of colorectal metastases Ann Surg 201210218
    1. BurrisIIIHAVogelCLCastroDMishraLSchwarzMSpencerSOakesDDKoreyAOrenbergEK1998Intratumoral cisplatin/epinephrine-injectable gel as a palliative treatment for accessible solid tumors: a multicenter pilot study Otolaryngol Head Neck Surg 118496503
    1. CarrB1996Escalating cisplatin doses by hepatic artery infusion (HAI) for advanced stage hepatocellular carcinoma (HCC)InSixth International Congress on Anticancer Treatment.376 (abstract)
    1. ColellaGBottelliRDe CarlisLSansaloneCVRondinaraGFAlbertiABelliLSGelosaFIamoniGMRampoldiADe GasperiACortiAMazzaEAseniPMeroniASlimAOFinziMDi BenedettoFManochehriFFolliniMLIdeoGFortiD1998Hepatocellular carcinoma: comparison between liver transplantation, resective surgery, ethanol injection, and chemoembolization Transpl Int 11S193S196
    1. CollinsJM1984Pharmacologic rationale for regional drug delivery J Clin Oncol 2498504
    1. CurleySAFuhrmanGMSiddikZHDavidsonBSClearyKRCromeensDM1995Direct intratumoral injection of a novel collagen matrix gel and cisplatin effectively controls experimental liver tumors Cancer Res Thera Con 4247254
    1. DavidsonBSIzzoFCromeensDMStephensLCSiddikZHCurleySA1995Collagen matrix cisplatin prevents local tumor growth after margin-positive resection J Surg Res 58618624
    1. FarrésMTde BaereTLagrangeCRamirezLRougierPMunckJ-NRocheA1998Percutaneous mitoxantrone injection for primary and secondary liver tumors: preliminary results CardioVasc Interven Radiolo 21399403
    1. FroelichJJRegnJIshaqueNHoppeMSaarBMauermannFKloseKJ1997Steuerung non-vaskulärer interventionsradiologischer Eingriffe mittels Echtzeit CT-Fluoroskopie Electromedica 655055
    1. Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire1995A comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma N Engl J Med 33212561261
    1. HayesDMCvitkovicEGolbeyRBScheinerEHelsonLKrakoffIH1977High dose cis-platinum diammine dichloride, amelioration of renal toxicity by mannitol diuresis Cancer 3913721381
    1. KemenyNLokichJAndersonNAhlgrenJ1993Recent advances in the treatment of advanced colorectal cancer Cancer 71918
    1. KemenyNE1995Regional chemotherapy of colorectal cancer Eur J Cancer 31A12711276
    1. LivraghiTGoldbergSNLazzaroniSMeloniFSolbiatiLGazelleGS1999Small hepatocellular carcinoma: treatment with radio-frequency ablation versus ethanol injection Radiology 210655661
    1. LorenzMStaib-SeblerEKochBGogCWaldeyerMEnckeA1997The value of postoperative hepatic arterial infusion following curative liver resection Anticancer Res 1738253833
    1. MillerBHShavinJSCognettaA1997Nonsurgical treatment approach for basal cell carcinomas with intralesional fluorouracil/epinephrine injectable gel J Am Acad Dermatol 367277
    1. OkudaKOhtsukiTObataHTomimatsuMOkazakiNHasegawaHNakajimaYOhnishiK1985Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients Cancer 56918928
    1. PattYZHoqueALozanoRPozdurRChaseJCarrascoHChuangVDelpassandESEllisLCurleySRohMJonesJrDV1997Phase II trial of hepatic arterial infusion of fluorouracil and recombinant human interferon alfa-2b for liver metastases of colorectal cancer refractory to systemic fluorouracil and leucovorin J Clin Oncol 1514321438
    1. RavoetCBleibergHGerardB1993Non-surgical treatment of hepatocarcinoma J Surg Oncol 3Suppl104111
    1. RougierPLaplancheAHayJOllivierJEscatJSalmonRJulienMRoulletJ-CGallotDGouziJPaillierJEliasDLacaineFRoosSRotmanSLuboinskiMLasserP1992Hepatic arterial infusion of floxuridine in patients with liver metastases from colorectal carcinoma: Long-term results of a prospective randomized trial J Clin Oncol 10112118
    1. SchlagPHohenbergerPHerfarthC1991Operative möglichkeiten und therapeutische chancen bei lebermetastasen Chirurg 62715.
    1. StanglRAltendorf HofmannACharnleyRMScheeleJ1994Factors influencing the natural history of colorectal liver metastases Lancet 34314051410
    1. TakayasuKMuramatsuYMoriyamaNHasegawaHMakuuchiMOkazakiNHirohashiSTsuganeS1989Clinical and radiologic assessments of the results of hepatectomy for small hepatocellular carcinoma and therapeutic arterial embolization for postoperative recurrence Cancer 6418481852
    1. VenookAP1997Update on hepatic intra-arterial chemotherapy (see comments) Oncology (Huntingt) 11947957discussion 961–962, 964, 970
    1. VoglTJMackMGStraubRMüllerPEichlerKEngelmannKFelixR1998MR-guided laser-induced thermotherapy of malignant liver lesions: technique and results Onkologie 21412419

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