Randomized, Phase II Trial of Pemetrexed and Carboplatin with or without Enzastaurin versus Docetaxel and Carboplatin as First-Line Treatment of Patients with Stage IIIB/IV Non-small Cell Lung Cancer

Abstract

There was no difference in TTP between the three arms, but survival was longer with pemetrexed-carboplatin compared with docetaxel-carboplatin. Enzastaurin did not add to the activity of pemetrexed-carboplatin.

The protein kinase C (PKC) inhibitors combined with chemotherapy in the treatment of advanced non-small cell lung cancer: meta-analysis of randomized controlled trials

“…In addition, limited evidence showed that the risk of grade 3/4 epistaxis was higher in PKC inhibitor-chemotherapy group (5.9 %) than chemotherapy alone group (1.2 %) (P = 0.022) [19]. Incidence of renal failure, hypokalemia, weight loss, hypertension, and diarrhea was similar between PKC inhibitors-chemotherapy groups (0.6, 2.8, 1.9, 12.5, 4.2 %) and chemotherapy groups (1.2, 0.6, 0.6, 22.2, 1.4 %) [11,18,19].…”

“…After reviewing the remaining six trials, we excluded one trial because of maintenance treatment with PKC inhibitor. Finally, five relevant RCTs, comprising a total of 1,005 patients, were included [10,11,[17][18][19]. The five RCTs contained the following two PKC inhibitors: enzastaurin (an inhibitor of PKC-b) and aprinocarsen (a PKC-a antisense oligonucleotide).…”

“…Thus, inhibition of specific isoenzymes of PKC may be a reasonable approach to achieve therapeutic benefit. Within the last decade, several small molecular weight inhibitors and antisense molecules have been developed, targeting the calcium-dependent classical isoforms of PKC, for the treatment of NSCLC, such as bryostatin I [6], UCN-01 [7,8], PKC412 [9], LY90003 [10], LY317615 [11], aurothiomalate (ATM) [12], and et al…”

A Phase II Randomized Study of Cisplatin-Pemetrexed plus either Enzastaurin or Placebo in Chemonaive Patients with Advanced Non-Small Cell Lung Cancer

“…Our findings also suggest that enzastaurin is tolerable when administered with full-dose cytotoxic chemotherapy, but because of the lack of additional efficacy with enzastaurin in the aforementioned studies [13,14], our patients remained in the study but continued treatment with cisplatin-pemetrexed or an alternative therapy of the physician’s choice.…”

“…The addition of enzastaurin to cisplatin/pemetrexed as first-line treatment in patients with advanced NSCLC was well tolerated, with no new or unexpected safety issues observed, and showed preliminary activity in the safety lead-in phase with 8 partial responses (1 unconfirmed). However, on the basis of the interim results from two other phase II, randomized trials of enzastaurin in patients with NSCLC [13,14], we decided to terminate the study early. These studies showed that the addition of enzastaurin to pemetrexed and to carboplatin-pemetrexed was well tolerated, with no new safety issues identified, but did not provide additional efficacy in patients with advanced NSCLC, and both studies were subsequently closed.…”