Phase I/II study with ruthenium compound NAMI-A and gemcitabine in patients with non-small cell lung cancer after first line therapy

Abstract

NAMI-A administered in combination with gemcitabine is only moderately tolerated and less active in NSCLC patients after first line treatment than gemcitabine alone.

Preclinical combination therapy of the investigational drug NAMI-A+ with doxorubicin for mammary cancer

“…It is doubtful that NAMI-A will be used as a mono-therapy for the treatment of human cancers and, thus, combination schedules with other antitumor drugs represent the optimum clinical approach. Indeed, the second clinical study performed with NAMI-A, following a phase I in which pharmacokinetic and host toxicity was defined, was performed in combination with gemcitabine for the treatment of metastasized NSCLCs [16]. This clinical study was selected because preclinical tests suggested a pronounced activity against lung metastases (Data on file, Callerio Foundation Onlus) and two patients with NSCLC in the previous phase I study showed prolonged disease stabilization [15].…”

“…More recently, NAMI-A completed a phase I/II study in combination with gemcitabine as a second line treatment for metastatic non-small cell lung cancer (NSCLC) [16]. The antimetabolite, gemcitabine, is one of the principal drugs used against NSCLC [17,18], frequently in combination with platinum-based drugs [19,20].…”

“…The phase II study was completed on 15 evaluable patients who showed a 60 % disease stabilization at 450 mg/m 2 NAMI-A combined with 1,000 mg/m 2 gemcitabine, given at cycles with NAMI-A on days 1 and 7 and gemcitabine on days 2 and 8, with a two-week washout between two consecutive cycles. Disease stabilization included a partial remission in one patient and stabilization in two patients treated with a more intense schedule of 300 mg/m 2 NAMI-A on days 1, 7 and 14 and 1,000 mg/m 2 gemcitabine on days 2, 8 and 15 [16].…”

The versatile ruthenium(II/III) tetraazamacrocycle complexes and their nitrosyl derivatives

“…Such complexes, including the indazolium ruthenium complex KP1019 (Fig. 17) and NAMI-A, have undergone phase I and II clinical evaluation for cancer with very limited side effects [193,196,205,230,[234][235][236][237]. Ru(II) complexes such as [RuCl 2 (2-phenylazopyridine) 2 ] (Fig.…”

The antimetastatic drug NAMI-A potentiates the phenylephrine-induced contraction of aortic smooth muscle cells and induces a transient increase in systolic blood pressure

“…Unlike platinum, with which, after more than 50 years, it still seems impossible to develop compounds to significantly outdo the potent antitumour activity of cisplatin, ruthenium compounds offer a generally accepted lower host toxicity [4,5] and an innovative mechanism of antitumour activity [6][7][8]. Among these new me-too drugs, imidazolium trans-imidazoledimethylsulphoxidetetrachlorido ruthenate (nicknamed NAMI-A) is the first in this class of drugs used to treat the metastatic non-small cell lung cancer (NSLCL) in humans in a second-line therapy in combination with gemcitabine [9]. NAMI-A is endowed with a unique ability to act against the metastases of solid tumours without necessarily reducing the tumour at its primary site [10,11], emphasizing the possibility of its being used in many chemotherapy protocols, typically applied in patients to prevent the formation of, or reduce the bulk of, the disseminated disease.…”