PACLITAXEL PLUS HYDROXYUREA AS 2ND LINE THERAPY FOR NONSMALL CELL LUNG-CANCER

We tested paclitaxel (Taxol(TM)) and low dose hydroxyurea as second li ne therapy in 30 patients with non-small cell lung cancer since both d rugs are active against non-small cell lung cancer in other settings, and since hydroxyurea may reverse chemotherapy resistance by disruptin g double minute chromosomes. Hydroxyurea 500 mg was given orally each Monday, Wednesday, Friday starting 1 week before paclitaxel, and conti nuing until removal from study. Paclitaxel 135 mg/m(2) was given i.v. over greater than or equal to 1 h every 3 weeks with dexamethasone, di phenhydramine, and ranitidine. Patients could have paclitaxel doses es calated to 175 mg/m(2) in course 2 and to 200 mg/m(2) in course 3, whe re tolerated. Sixteen males and 14 females were treated. All patients had previously received a single cisplatin-based chemotherapy regimen and 23 had previously received radiotherapy. Twelve patients had adeno carcinomas, six had squamous cell carcinomas, and 12 had large cell ca rcinomas. Eight patients had Stage IIIb cancers and 22 had Stage IV. P aclitaxel doses were 135 mg/m(2) in 56 courses, 175 mg/m(2) in 24, and 200 mg/m(2) in 15. Treatment was well tolerated. Median granulocyte n adirs were 2.5 (x 10(9)/1) for paclitaxel 135 mg/m(2), 1.8 for 175 mg/ m(2), and 1.3 for 200 mg/m(2). No patient developed febrile neutropeni a, and none required a dose reduction. Two patients had reversible ana phylaxis. Other toxicities were quite tolerable, They included fatigue , myalgias, dizziness, paresthesias, diarrhea, alopecia, mucositis, fl ushing, headache, swollen red hands, and anxiety. One patient had a pa rtial remission and 15 had stable disease (including six with minor re sponses). Median survival was 20 (95% CI, 12-34) weeks, with 19% of pa tients remaining alive at 1 year from initiation of treatment. This is a well-tolerated regimen with modest activity as second line chemothe rapy for patients with non-small cell lung cancer previously treated w ith cisplatin regimens. Higher doses would be feasible and other strat egies are now being explored.