Phase I trial of PT-100 (PT-100), a cytokine-inducing small molecule, following chemotherapy for solid tumor malignancy

Cancer Invest. 2006 Oct;24(6):553-61. doi: 10.1080/07357900600894732.


PT-100 upregulates cytokine expression competitively inhibiting the dipeptidyl peptidase activity of fibroblast activation protein (FAP) and dipeptidyl peptidase IV (DPP-IV). This dose-escalation study was conducted to evaluate the safety of PT-100 in patients receiving myelosuppressive chemotherapy and to assess its effects on neutrophil recovery.PT-100 was administered orally for 7 days as a 200 microg, 400 microg, 800 microg, or 1,200 microg total daily dose (divided twice daily) to 6, 6, 17, and 5 patients, respectively. Patients received 2 cycles of chemotherapy: The first cycle served as each individual patient's control. Patients had to develop Grade 3+ neutropenia in Cycle 1 in order to receive PT-100 in Cycle 2. Most patients received PT-100 on Days 2-8 of chemotherapy in Cycle 2, except at 800 microg where an additional cohort (n = 8) was treated on a Days 5-11 schedule. Five of 7 patients receiving 800 microg on Days 2-8 experienced a >/=1-day improvement in Grade 3+ neutropenia in Cycle 2 versus Cycle 1. Overall, PT-100 was well tolerated. A reduction in chemotherapy-related nausea, vomiting, fatigue, alopecia, and diarrhea was noted in patients receiving PT-100. Edema/peripheral swelling, hypotension, hypovolemia, and dizziness were the most common nonhematologic adverse events considered related to PT-100. Two Grade 3 adverse events were considered related to PT-100: syncope (1,200 microg) and orthostatic hypotension (800 microg). A maximum tolerated dose was not reached. Given the accelerated neutrophil recovery, preclinical evidence of antitumor activity, and tolerable toxicities of PT-100, additional studies to optimize the PT-100 dosing schedule in patients receiving myelosuppressive chemotherapy are needed.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Boronic Acids / pharmacokinetics
  • Boronic Acids / therapeutic use*
  • Cytokines / metabolism*
  • Dipeptides / pharmacokinetics
  • Dipeptides / therapeutic use*
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / antagonists & inhibitors
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasms / drug therapy*
  • Salvage Therapy
  • Treatment Outcome


  • Boronic Acids
  • Cytokines
  • Dipeptides
  • PT-100 dipeptide
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases