Biomedical Engineering Reference
In-Depth Information
Tumors are generally treated using combination therapies such as chemother-
apy, radiation and surgery. Paclitaxel could be used as an adjuvant to any of these
as discussed in the non-clinical studies, but it was reported that 18- to 24-h incu-
bation with paclitaxel was needed to sensitize the cancer cells to radiation [
21
,
22
]. Moreover, this sensitivity was only effective for a short period of time and
declined rapidly after removal of paclitaxel [
23
]. Thus, Oncogel™ was found to
meet this specification as it presented a sustained release of paclitaxel for a period
of 6 weeks, which could increase the efficacy of radiotherapy.
3.3.1 Esophageal Cancer
The number of annual deaths caused by esophageal cancer is estimated to be about
300,000 [
24
]. The scenario is complicated by the fact that the 50 % of diagnosis
is usually made when the disease is in its final stages. As the phase 1 studies illus-
trated the lack of any significant systemic circulation of paclitaxel, Oncogel™ was
recognized as a potential alternative to the morbidity inducing treatment options
like chemotherapy, radiotherapy and surgery. A multi-national US phase 2a dose
escalation study was conducted to evaluate the efficacy of a dual therapy regi-
men (Oncogel™
+
RT) on patients suffering from advanced esophageal disease
without having undergone chemotherapy. Oncogel™ of varying concentrations
(1.5, 3.1 and 6.3 mg/ml) was successfully injected using linear EUS guidance.
Patients were subjected to 28 fractions of 1.8 Gy radiation 3 days after the injec-
tion. No dose limiting toxicities was observed and Oncogel™ did not add on to
the risks of RT. The pharmacokinetics of paclitaxel was also uninfluenced by the
presence of radiation. However, caution must be exercised while making the com-
parison since the study involved no cohort of patients undergoing only radiation
therapy. The intratumoral concentration of Oncogel™ was reported to be 0.48,
1.0, and 2.0 mg paclitaxel per cm
3
of tumor [
6
,
12
]. Peak plasma concentrations
was related to the Oncogel™ concentration and ranged from 0.53 to 2.73 ng/ml.
Oncogel™ was well tolerated in the body; 82 % of the patients (n
=
11) were
found to show an improvement in dysphagia over the study period. On a 5 point
scale, 55 % had a two point improvement and three had a one point improvement.
The efficacy results were positive; 2 patients were reported to have a progres-
sive response, whereas 6 patients were classified as having a stable disease and
two under progressive disease. The biopsies collected at the end of week 11 were
negative for 4 patients and two patients with stage 3 disease showed significant
improvements and were considered for resection. The phase 2b study has tumor
response as the primary end point, whereas the safety, survival and pathological
complete response (pCR) of the tumor was the secondary endpoints. It designed a
control group comprising of patients receiving standard of care-(5-FU), cisplatin
and RT (chemo radiotherapy) and the treatment group consisted of patients with
Oncogel™ and chemo radiotherapy. Though the combination of Oncogel™ plus
chemo radiotherapy increased the number of adverse events, overall the therapy
was well tolerated. But the overall response of the Oncogel™ treatment group was
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