Phase I dose escalation trial of biweekly pemetrexed in combination with docetaxel in advanced solid tumors

Abstract

13019 Background: Pemetrexed (PEM) and docetaxel (DOC) are cytotoxic agents with a broad range of activity in solid tumors and relatively non-overlapping toxicities. We are conducting a single site dose escalation trial of biweekly dosing of PEM + DOC in advanced solid tumor patients (pts) to determine the maximum tolerated dose (MTD), dose limiting toxicities (DLTs), and preliminary antitumor activity for the combination. Eligible pts have had 0–1 prior therapies, a performance status of 0–1, and creatinine clearance of =45 ml/min. Methods: Escalating doses of PEM (10 min infusion, d1 and 15) and DOC (1 hr infusion, d1 and 15) are administered q 28 days. Pretreatment vitamin supplementation consists of 1 mg IM vitamin B12 repeated q 9 weeks and daily oral folate 350–1,000 mcg. DLT is defined as grade 4 neutropenia =5 days, febrile neutropenia, grade 4 thrombocytopenia, or grade 3–4 non-hematological toxicity in cycle 1. Results: To date, 12 pts ages 40–70 have been enrolled at 3 dose levels. Tumor types (N pts) include leiomyosarcoma (3); schwannoma (1); synovial sarcoma (1); transitional cell carcinoma of the bladder (1) and non-small cell lung carcinoma (NSCLC) (6). One patient was withdrawn for early progressive disease. Grade 3/4 treatment-emergent toxicities for 11 pts include neutropenia (3), anemia (1), mucositis (1), hyperglycemia (1), anorexia (1), weight loss (1), hyponatremia (1), pain (1), dehydration (1), fatigue (1), and thromboembolism (1). In addition, one pt had grade 5 pneumonitis during cycle 3. Dose level 3 has been expanded due to DLT in 1 pt. Antitumor activity for 11 evaluable pts includes 2 confirmed partial responses (by RECIST) in uterine leiomyosarcoma after adjuvant AIM therapy and pretreated NSCLC; stable disease in 5 pts; and progressive disease in 4 pts. Conclusion: Biweekly dosing of PEM + DOC is feasible and shows activity in a number of advanced solid tumors. The MTD has not been reached. *Pt with early progression replaced [Table: see text] No significant financial relationships to disclose.