American Society of Clinical Oncology: Pemetrexed (Alimta) and Gemcitabine (Gemzar) plus Platinum

Posted by James

In stage IIIB/IV non-small-cell lung cancer (NSCLC), the combination of pemetrexed (Alimta, Eli Lilly) plus carboplatin (Paraplatin, Bristol-Myers Squibb) as a first-line chemotherapy produced significantly less toxicity than the combination of gemcitabine (Gemzar, Eli Lilly) plus carboplatin. In addition, patients receiving the pemetrexed/carboplatin (Pem/Carbo) regimen needed fewer transfusions than those receiving the gemcitabine/carboplatin (Gem/Carbo) combination.

This finding emerged from a clinical trial among 537 patients with NSCLC conducted by Dr. Gronberg. Noting that platinum-based doublets are considered standard treatment in these patients, he said that the rationale for the trial was that phase 2 trials had suggested that pemetrexed plus a platinum agent might be equally effective as standard doublets but with a more favorable toxicity profile.
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He explained: “Pemetrexed is easy to administer and might provide a better quality of life to this population with poor performance status and significant comorbidity.”

Patients (median age 65 years, 57.5% male) were randomly assigned to receive four three-week cycles of either (1) pem-etrexed 500 mg/m² plus carboplatin (with an area-under-the curve [AUC] concentration of 5) (Pem/Carbo) or (2) gem-citabine 1,000 mg/m² plus carboplatin (with an AUC concentration of 5) (Gem/Carbo).

Both patient groups received vitamin supplementation. Patients who were 75 years of age and older received 75% of the dose.

Among grade 3 and 4 toxicities, leukopenia (22%/44%, respectively), granulocytopenia (38%/48%), and thrombocyto-penia (24%/54%) were all significantly higher with Gem/Carbo. The need for blood transfusions and platelet transfusions (28%/42%) was significantly lower with Pem/Carbo (3%/9%).

Median overall survival was similar for the two groups: 7.3 months with Pem/Carbo and 7.0 months with Gem/Carbo. buy antibiotics amoxicillin

Dr. Gronberg suggested, “While there were no differences in overall survival, patients receiving Pem/Carbo experienced significantly less toxicity.”

Enzastaurin

Both protein kinase-C (PKC) and P13k (phosphatidylinosi-tol 3-kinase)/AKT are overexpressed and overactive in lung cancer tissues and cell lines. Enzastaurin is an oral serine/ threonine kinase inhibitor that targets the PKC and P13/AKT pathways, inducing tumor apoptosis. It also inhibits tumor cell proliferation and suppresses tumor-induced angiogenesis.

Dr. Bepler presented a phase 2 study among patients with NSCLC whose disease had progressed after one or two previous therapies.

Patients (n = 55) received oral enzastaurin 500 mg once daily for a planned maximum duration of six cycles of 28 days each. The participants had received at least one prior regimen, at least one of which was platinum-based.

The mean age of the patients was 63 years, 55% were men, and 78% had stage IV disease. Most patients (62%) completed between two and six enzastaurin cycles. The primary study objective was to estimate progression-free survival at six months.

At a six-month interim analysis, the median progression-free survival time was 1.8 months, and the rate of progression-free survival was 13%. Best overall response assessment among 48 patients continuing therapy showed stable disease in 19 patients (34%) and progressive disease in 29 patients (53%). The median overall survival time was 1.8 months, and the rate of 12-month overall survival was 44%. No objective tumor responses were observed.

Enzastaurin was well tolerated. Fatigue was the most common drug-related toxicity, reported at rates of 14.5% for grade 1 toxicities, 12.7% for grade 2, and 3.6% for grade 3. Fatigue was observed in patients whose disease progressed but not in patients whose disease had stabilized. Five patients died of non-drug-related causes during the study. Two of the deaths were attributed to disease progression. canadian pharmacy viagra

“Long-term disease stabilization in three patients who had progressed after one or two prior therapies suggests enzastau-rin may have activity in NSCLC,” Dr. Bepler said.

Although the rate of disease stabilization was modest, one patient was treated for 20 months before disease progression, and six patients were treated for longer than six months.

He summarized as follows: “This is an oral drug [associated] with only minor fatigue. With molecular markers, perhaps PKC via immunohistochemistry, we may be able to select those patients more likely to respond.”