Glutoxim, a disulfide-containing hexapeptide, ensures a favorable survival outcome and better tolerability of chemotherapy in patients with stage III-IV non-small-cell lung cancer.
Kozhemyakin LA., Smirnov A.I., Orlov S.V. Pulmonology Research Institute of Saint-Petersburg State Pavlov Medical University, St-Petersburg, Russia, Novelos Therapeutics, Inc., USA.
Glutoxim, a hexapeptide with a stabilized disulfide bond, has been shown
to possess multicytokine-activating and hematopoietic properties and has been
recently approved for medicinal use in the
Study Population and Dosing Regimens.
By now the clinical data on NSCLC patients treated with Glutoxim have been collected for more than 200 individuals. About 60 of them received Glutoxim as an add-on treatment in the framework of the 2 above mentioned prospective randomized studies, while findings on more than 140 other patients have been analyzed retrospectively as observational cases. The patients randomized into the control groups of the prospective randomized studies were treated with chemotherapy alone (cisplatin - etopozid regimens). The subjects randomized into the active treatment arms received identical chemotherapy regimens combined with Glutoxim applied as intravenous or intramuscular injections (30-90 mg. daily). The other 140 patients received treatment with Gluloxim (30-120 mg) combined with various chemotherapy regimens and sometimes with radiotherapy applied before or after the chemotherapy. These observational data have been analyzed against a retrospectively compiled control group of 118 patients who received chemo- or chemo- plus radiotherapy without Glutoxim.
The analysis performed for the 2 prospective randomized studies and for
retrospective observations have revealed certain trends in safety and efficacy
profiles of Glutoxim, which proved to be common for all 3 patient cohorts.
First, there have been no study related adverse events, laboratory
abnormalities or incompatibility with any other class of medicines used in the
treatment of cancer patients. Second, patients treated with Clutoxim
experienced less prominent hemodepression in response to the chemotherapy and
faster hematopoietic recovery than in the control group. This mitigation by
Glutoxim of the sine- ejects associated with chemotherapy prevents
treatment-related complications and allows patients to receive additional
courses of chemotherapy more frequently. Thus, patients treated with Glutoxim
were able to tolerate more chemotherapy courses and higher doses of the anticancer
drugs. Third, a measurable tumor response was detected for a greater number for
sequential chemotherapy courses, with the overall response being more prominent
for the Glutoxim groups than in the control ones. Finally, a survival analysis
for the first prospective randomized study showed that by the end of 1-year
follow-up just 5 patients out of 30 available control subjects (16.7%) had
survived, while in the Glutoxim group there had been 24 patients out of the 38
available, who had survived for 1 year (63.2%).
The above results will be discussed in the context of other recently collected clinical and experimental data on interaction of disulfide-containing peptides with intracellular regulatory mechanisms of normal and cancer ceils (RAS signaling cascade, MDR-. p53-, and p21-gene systems' and redox-dependent transcription factors).
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