Paclitaxel is a natural product with anti-tumor activity. It binds to tubulin, inducing polymerization and paralyzation of the mitotic spindle. This interruption prevents replication of neoplastic cells. It is one of the most active agents available for breast and ovarian cancer. Prior studies using paclitaxel for previously treated NHL have demonstrated modest activity with overall response rates (ORR) from 17-25%. This study is performed to determine the clinical activity and toxicity profile of weekly, low-dose paclitaxel in previously treated NHL. Patients considered for this trial are typically heavily pretreated with poor marrow reserve or elderly with co-morbidities precluding more aggressive treatments. All NHL subtypes are eligible and there are no restrictions on the number of prior therapies. PS 0-3 is allowed. The treatment plan is paclitaxel 90 mg/m2 weekly over 1 hour x 6 weeks. Patients receive a two week rest period with restaging. Patients with progressive disease (PD) come off study. Patients with stable disease or any response repeat the 6 week course until complete response (CR), PD or unacceptable toxicity. To date, 17 patients have been enrolled with 13 évaluable for toxicity and 12 évaluable for response. The 13 évaluable patients have the following characteristics; 10/14 male, mean age 65 (44-85), mean IPI 2.6 (1-5), mean # prior therapies 4 (2-8), and 10/14 refractory to most recent prior therapy. The ORR is 33% (4/12) with 3 partial responses and 1 CR. The patient inevaluable for response developed PCP pnuemonia 3 weeks into treatment and was taken off study. The toxicity profile of the other 12 patients is as follows: Hématologie - 1 grade 3 pit, 1 grade 3 ANC, 1 grade 2 pit, 1 grade 1 ANC; Neurologic -2 grade 3 (sensory), 2 grade 2 ( 1 sensory, 1 motor), and 1 grade 1. The two patients with grade 3 neuro toxicity were removed from the study with subsequent improvement to grade 2. Conclusion: Weekly, low-dose paclitaxel is a good means of palliation for individuals with previously treated NHL who are not candidates for more aggressive therapy. The major toxicity is neurologic. Myelosuppression is minimal, making this dosing schedule attractive for further development in combination with other agents. Accrual to this study continues.
|Issue number||11 PART II|
|State||Published - Dec 1 2000|