As I read this, it means that 2 of 14 patients have had a >50% drop, and "several" others have stabilized. (Just how much is "several" anyway?)
This is indeed good news, as dropping PSA levels are generally correlated with increased survival (see abstract). By way of comparison and to stop people getting over-enthusiastic however, I have also included two abstracts related to topotecan Phase II studies of hormone refractive prostatic cancer.
One abstract shows 6/34 with >50% PSA reduction (comparable to MGI-114) and concludes it has "limited activity," while the other says it has no activity.
Peter
J Clin Oncol 1998 May;16(5):1835-43
Change in serum prostate-specific antigen as a marker of response to cytotoxic therapy for hormone-refractory prostate cancer.
Smith DC, Dunn RL, Strawderman MS, Pienta KJ
Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, USA. dcsmith@umich.edu
PURPOSE: Prostate-specific antigen (PSA) has been used as a marker of advanced prostate cancer but remains controversial. To evaluate PSA as a predictor of survival, we analyzed data from sequential phase II trials of estramustine and etoposide. METHODS: A landmark analysis that used data from 62 men with PSA levels at baseline and 8 weeks was conducted. The best PSA measure (of six evaluated) was incorporated into a multiple regression model with performance status (PS); relative change in PSA level; and pretreatment PSA, alkaline phosphatase, and hemoglobin values. RESULTS: A decrease in PSA of 50% or greater at 8 weeks was associated with a significantly increased survival (P=.0005, two-sided log-rank test). Median survival from the landmark was 91 weeks in patients with a 50% or greater decrease at 8 weeks versus 38 weeks in those without this decrease. Modeling showed that PS, pretreatment hemoglobin level, and relative change in PSA level were significant prognostic factors, with a significant interaction between PS and pretreatment hemoglobin level. In the final model, a relative change in PSA level at 8 weeks of less than 50% had an adjusted relative risk of 2.20 (95% confidence interval, 1.21 to 4.00). A decrease in PSA level of 50% or greater at any time during therapy was associated with a response in measurable disease (P=.0369, two-sided Fisher's exact test). CONCLUSION: The PSA value after 8 weeks of this cytotoxic regimen does predict survival. A decrease in PSA level is associated with both survival and response in soft tissue lesions and should be incorporated into the response criteria and reporting of trials of cytotoxic agents in prostate cancer.
Invest New Drugs 1995;13(3):235-40
Phase II study of topotecan in metastatic hormone-refractory prostate cancer.
Hudes GR, Kosierowski R, Greenberg R, Ramsey HE, Fox SC, Ozols RF, McAleer CA, Giantonio BJ
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
Systemic chemotherapy with currently available agents has not improved survival for patients with hormone refractory prostate cancer (HRPC), consequently, the evaluation of new agents is warranted. Topotecan is a specific inhibitor of topoisomerase I with broad antitumor activity in preclinical studies. The purpose of this phase II trial was to determine the objective response rate of topotecan administered as a 30 minute infusion for five consecutive days in men with metastatic HRPC. Thirty-four evaluable patients were treated with topotecan 1.1-1.5 mg/m2 as a 30 minute infusion daily for five days, repeated every three weeks until disease progression or unacceptable toxicity. Response was assessed with a combination of standard solid tumor response criteria and the serum prostate specific antigen (PSA) for patients with bidimensionally measurable disease, and by serial measurements of the PSA in patients with bone only (evaluable) disease. One of 13 patients (7.6%) with measurable soft tissue disease had a PR in nodal sites. Of 21 patients with only osseous metastases, 1 (4.7%) had improvement in bone scan. Six of the 34 evaluable patients (17.6%) had the serum PSA decrease by > or = 50% and 2 (5.8%) had PSA decreases of > or = 75%. Toxicity was chiefly hematologic with 66% of patients experiencing Grade 3 or 4 granulocytopenia. Thirty-nine percent of cycles required a delay to allow for hematologic recovery and ten patients required red cell transfusions. Non-hematologic toxicity, mainly nausea and alopecia, was mild. Topotecan administered at this dose and schedule has limited activity in patients with HRPC. Further trials of topo I inhibition in HRPC should utilize alternative schedules of topotecan (e.g., prolonged infusion) or other camptothecin analogs with more potent topo I inhibitory activity.
Anticancer Drugs 1996 Jun;7(4):410-4
A phase II trial of topotecan in patients with previously untreated pancreatic cancer.
O'Reilly S, Donehower RC, Rowinsky EK, Ord S, Grochow LB
Division of Pharmacology and Experimental Therapeutics, Johns Hopkins Oncology Center, Baltimore, MD 21287-8934, USA.
Because currently available chemotherapeutic agents are largely ineffective in the treatment of pancreatic cancer, novel treatments are urgently needed to improve outcomes in this disease. The purpose of this phase II study was to evaluate the anti-tumor activity of topotecan, a hydrophilic camptothecin analog that has demonstrated a wide range of anti-tumor activity in preclinical and phase I studies. Topotecan was administered as a 30 min infusion at a dose of 1.5 mg/m2/day for five consecutive days every 3 weeks, to chemotherapy-naive patients with advanced pancreatic cancer. Neutropenia was the principal toxicity of topotecan on this dosing schedule. No significant anti-tumor responses were observed in 27 patients with measurable disease. The median time to disease progression was 7 weeks and the median survival duration was 17.5 weeks. Thus, topotecan, administered on this schedule, is ineffective for patients with pancreatic carcinoma. |
