Intratumoral cisplatin/epinephrine‐injectable gel as a palliative treatment for accessible solid tumors: A multicenter pilot study

Burris, A. Howard; Vogel, Charles L.; Castro, Dan J.; Mishra, Lopa; Schwarz, Manfred; Spencer, Sharon; Oakes, David D.; Korey, Andrew; Orenberg, Elaine K.

doi:10.1177/019459989811800412

Cited by 56 publications

(20 citation statements)

References 26 publications

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“…Several cytostatic agents, including fotemustine (Schallreuter et al, 1991), bleomycin (Glass et al, 1996;Heller et al, 1998), and cisplatin (Burris et al, 1998) have been used intralesionally, with varying results. As immune mechanisms have been shown to play a significant role in the pathogenesis and clinical course of melanoma (reviewed in Curiel- Lewandrowski and Demierre, 2000), a number of reports have addressed the treatment of melanoma metastases with intralesionally injected immunemodulatory cytokines, including interferon- alpha (von Wussow et al, 1988), interferon-beta (Fierlbeck et al, 1992;Umeda et al, 1998;Cornejo et al, 2000), and GM-CSF (Vaquerano et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…The therapeutic value of several intralesionally administered cytostatic agents and cytokines, such as fotemustine (Schallreuter et al, 1991), bleomycin (Glass et al, 1996;Heller et al, 1998), cisplatin (Burris et al, 1998), interferon-alfa (von Wussow et al, 1988), interferon-beta (Fierlbeck et al, 1992;Umeda et al, 1998;Cornejo et al, 2000), and GM-CSF (Vaquerano et al, 1999) has been investigated with varying outcome. However, none of these therapies has yet been shown to be a convincing alternative to conventional therapies.…”

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confidence: 99%

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Phase II trial of intralesional therapy with interleukin-2 in soft-tissue melanoma metastases

et al. 2003

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The objective of the present study was to validate the use of intralesional injection of interleukin-2 (IL-2) in patients with skin and softtissue melanoma metastases. A total of 24 patients with AJCC stage III or IV melanoma and single or multiple skin and soft-tissue metastases were included. Interleukin-2 injections were administered intralesionally into the total number of cutaneous and soft-tissue metastases accessible from the skin, 2 -3 times weekly, over 1 -57 weeks. Single doses varied from 0.6 to 6 Â 10 6 IU, depending on lesion size. The clinical response was monitored by sonography and confirmed by histopathology; response evaluation was confined to the intralesionally treated tumours. Complete response (CR) of the treated metastases was achieved in 15 patients (62.5%), the longest remission lasting 38 months to date. In five patients, partial response (PR) was achieved (21%) and in another three patients, progressive disease was observed (one patient not assessable). A total of 245 metastases were treated with CR in 209 (85%), and PR in 21 (6%). The therapy was generally well tolerated; the observed adverse events were mainly of grade 1 -2 severity. Immunohistochemical studies showed the tumour cells undergoing apoptosis and revealed a mixed character of the inflammatory infiltrate. The unusual high CR rate in metastatic melanoma of 62.5% and the limited toxicity suggest that treatment of skin and softtissue melanoma metastases with intralesional injection of IL-2 may be a safe and effective alternative to conventional therapies. The optimal dosage and duration of this therapy still remain to be defined in larger prospective multicentre trials.

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Section: Discussionmentioning

confidence: 99%

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Phase II trial of intralesional therapy with interleukin-2 in soft-tissue melanoma metastases

et al. 2003

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“…In preclinical studies, conventional chemotherapeutic agents such as cisplatin, fluorouracil, or vinblastine administered intratumourally in the gel formulation enhanced drug retention and increased antitumoural efficacy . Injectable gels have been used to treat various spontaneous tumours in veterinary patients and human malignancies such as basal and squamous cell carcinomas and accessible solid tumours of various histologic types (Miller et al, 1997;Burris et al, 1998). A recent french study showed development of therapy-induced necrosis after percutaneous intratumoural injections of mitoxantrone in primary and secondary liver malignancies (Farrés et al, 1998).…”

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

et al. 2002

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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/epinepthrine 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.

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“…Intratumoural platinum concentrations 10 to 100 times those after systemic cisplatin treatment have been recorded for 1 to 3 days (Yu et al, 1995). In clinical experience with CDDP/epi gel in solid tumours, adverse effects typical of systemically administered cisplatin were rare and mild (Burris et al, 1998). Efficacy and clinical benefit of the drug for local tumour control has been demonstrated in phase II open-label trials for a variety of solid tumours including cutaneous and soft tissue metastases of malignant melanoma (Oratz et al, 2002), recurrent breast cancer (Roshon, 2001), oesophageal (Harbord et al, 2002), and gastric cancer (Monga et al, 1998), and primary and secondary malignant liver tumours (Leung et al, 2001;Thuluvath et al, 2001;Vogl et al, 2002).…”

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A phase III placebo-controlled study in advanced head and neck cancer using intratumoural cisplatin/epinephrine gel

et al. 2002

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Patients with recurrent or refractory head and neck squamous cell carcinoma received cisplatin/epinephrine injectable gel or placebo gel injected directly into the clinically dominant tumour. The double-blind phase III trial comprised of up to 6 weekly treatments over 8 weeks, 4 weekly evaluation visits, and then monthly follow-up; open-label dosing began as needed after three blinded treatments. Tumour response was defined as complete (100% regression) or partial (50 -99% regression) sustained for 528 day, and patient benefit as attainment of palliative or preventive goals prospectively selected by investigators and patients. With cisplatin/epinephrine gel, 25% (14 out of 57) of tumours responded (16% complete regression, 9% partial regression), vs 3% (one out of 35, complete regression) with placebo (P=0.007). Patient benefit was positively associated with target tumour response in the blinded period among cisplatin/epinephrine gel recipients (P=0.024): 43% (six out of 14) of responders benefited, vs 12% (five out of 43) of non-responders. The most frequent adverse event was pain during injection and the next most frequent was local cytotoxic effects consistent with the gel's mode of action. Systemic adverse events typical of intravenous cisplatin were uncommon. Intratumoural therapy with cisplatin/epinephrine gel provided safe, well-tolerated, effective palliative treatment for patients with locally advanced head and neck squamous cell carcinoma, who lack other satisfactory treatment options.

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Intratumoral cisplatin/epinephrine‐injectable gel as a palliative treatment for accessible solid tumors: A multicenter pilot study

Cited by 56 publications

References 26 publications

Phase II trial of intralesional therapy with interleukin-2 in soft-tissue melanoma metastases

Phase II trial of intralesional therapy with interleukin-2 in soft-tissue melanoma metastases

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

A phase III placebo-controlled study in advanced head and neck cancer using intratumoural cisplatin/epinephrine gel

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