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Human Studies
Summary of most recent novel cancer therapy and pain treatment
study (Cura et al, 2002) Phase I
human clinical and pharmacokinetic studies on Crotoxin.
A Phase I clinical trial of crotoxin was performed at the Dept. of Medical Oncology Hospital San Martin, Parana,
Entre Rìos, Argentina and published in the journal "Clinical Cancer Research". Twenty-three (23) patients were
evaluated after the administration of crotoxin as a daily intra-muscular injection for 30 consecutive days
(1-3 cycles) at doses up to 0.9mg. No drug-related deaths occurred in this study and no significant toxicity was
observed up to a dose level of 0.4mg. Injection site reactions and double vision were the most characteristic side
effects observed. No impairment of respiration was observed. Four patients did not complete the trial for
differing reasons. With respect to the drug, one patient had an anaphylactoid reaction on study day 30 and was removed
from the protocol. The maximum tolerated dose (MTD) was 0.9 mg. Eighteen out of the 23 patients reported a progressive
but significant decrease or disappearance of pain (associated mainly with bone metastases) commencing on the second or
third week of the treatment. The reduction in pain was also reflected by the decrease in consumption of analgesics.
This effect was noted regardless of disease progression.
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Regarding the efficacy of the drug, the presence of objectively measurable lesions was not included as a requirement
for patient enrolment in this study. Some observations with regard to drug related effects were noted. There was no
disease progression observed in 4 patients. Objectively measured partial responses were observed in 3 patients.
Patient No. 18 had a thyroid carcinoma of 4 x 3.5 x 3.5 cm. Treatment with crotoxin reduced the dimensions of the
tumour mass to 2.5 x 1.5 x 1.5 cm. Patient No. 16 had a rectal carcinoma with pelvic invasion. A CT study showed a
tumour mass of 6.4 x 5.8 x 4.2 cm. Treatment with crotoxin reduced the dimensions to 4.0 x 2.2 x 1.8 cm and the
tumour mass was removed surgically. Patient No. 21 (breast cancer with lung metastases and pleural effusion) treated
with crotoxin presented a complete response in less than 4 months, without any weight loss, that lasted 6 months after
suspension of the treatment.
J E Cura, D P Blanzaco, C B Brisson, M A Cura, R Cabrol, L Larrateguy, C Mendez, J C Sechi, J S Silveira,
E Theiller, A R deRoodt and J C Vidal: Phase I and Pharmacokinetic study of Crotoxin (Cytotoxic PLA2, NSC-624244) in
Patients with Advanced Cancer. Clinical Cancer Research, Vol. 8, 1033-1041 (2002)
In the second study Costa et al. (1998) report their clinical experience with VRCTC-310 in two patients suffering with
advanced cancer in which the skin was severely compromised. VRCTC-310 is a combination of the snake venoms crotoxin
(CT) and cardiotoxin (CD). The local (peritumoral) treatment with the drug (0.014 mg/kg/week during 6 weeks) provoked
the complete disappearance of a relapsed skin squamous cell cancer in one patient. The other patient was an aged woman
with local-advanced breast cancer (carcinoma en cuirasse) who was inoculated intra-and-peritumoral with VRCTC-310.
After 6 weekly courses (0.014 mg/kg/week) with the drug a > 80% tumor reduction was seen. A 133 days follow-up
demonstrated not only an objective complete response of the primary tumor mass, but the disappearance of supraclavicular
tumor mass as well a significant reduction in lymphangitis.
Costa LA, Miles F, Araujo CE, Gonzalez S, and Villaruba VG: Tumor regression of advanced carcinoma following
intra-and/or peri-tumoral inoculation with VRCTC310 in humans: preliminary report of two cases, Immunopharmacol.
Immunotoxicol. 20 (1), 15-25 (1998)
A phase I study was performed to evaluate the maximum tolerated dose (MTD), safety profile and pharmacokinetic data
with VRCTC-310 (Costa et al., 1997). Fifteen patients with refractory malignancies were entered after providing written
informed consent. VRCTC-310 was administered as an intramuscular injection daily for 30 consecutive days. Doses were
escalated from 0.0025 to 0.023 mg/kg. Toxicities included local pain at the injection site, eosinophilia, reversible
diplopia and palpebral ptosis. Dose escalation was stopped at 0.023 mg/kg, when two patients had developed
anaphylactoid reactions. Both cases had high drug-specific IgG by EIA. MTD was 0.017 mg/kg and the recommended dose
for phase II studies is 0.017 mg/kg. Stabilization was found in six patients.
Costa LA, Miles F, Diez RA, Araujo CE, Coni Molina CM and Cervellino JC; Phase I study of VRCTC310, a purified
phospholipase A2 purified from snake venom, in patients with refractory cancer: safety and pharmacokinetic data,
Anticancer Drugs 8 (9), 829-34 (1997)
Cancer Types Observed in Participating Patients
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