A phase I trial of SJG-136 (NSC#694501) in advanced solid tumors

Cancer Chemother Pharmacol. 2010 Apr;65(5):833-8. doi: 10.1007/s00280-009-1088-4. Epub 2009 Aug 12.


Purpose: SJG-136 is a pyrrolobenzodiazepine dimer that forms DNA crosslinks and has demonstrated broad antitumor activity. We undertook this trial to determine the maximum-tolerated dose (MTD), toxicities and pharmacokinetic (PK) profile of SJG-136 in patients with an advanced solid tumor.

Patients and methods: In this phase I study, patients were treated with SJG-136 on days 1, 8 and 15 of a 28-day cycle. Dose levels studied were 10, 20, 40 and 60 microg/m2. PK parameters of SJG-136 were assessed following the intravenous administration of SJG-136 on days 1 and 15 of cycle 1.

Results: Twenty-one patients with advanced solid tumors were treated. Patients had a median of two prior chemotherapy regimens. Fatigue was dose-limiting with SJG-136 60 microg/m2/day administered on days 1, 8 and 15 of a 28-day cycle. Grade 3 thrombocytopenia and delayed onset liver toxicity were seen in one patient each. PK parameters of SJG-136 indicated dose-proportional increases in systemic exposure with increasing doses. No objective responses were seen.

Conclusion: For patients with advanced solid tumors, the MTD of SJG-136 is 40 microg/m2/day administered on days 1, 8 and 15 of a 28-day cycle. The major dose limiting toxicity was fatigue. Alternative dosing strategies are now being evaluated.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Benzodiazepinones / administration & dosage*
  • Benzodiazepinones / adverse effects
  • Benzodiazepinones / pharmacokinetics
  • Colonic Neoplasms / drug therapy
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Tolerance
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Male
  • Maximum Tolerated Dose
  • Melanoma / drug therapy
  • Middle Aged
  • Ovarian Neoplasms / drug therapy
  • Pyrroles / administration & dosage*
  • Pyrroles / adverse effects
  • Pyrroles / pharmacokinetics
  • Urinary Bladder Neoplasms / drug therapy


  • 1,1'-((propane-1,3-diyl)dioxy)bis(7-methoxy-2-methylidene-1,2,3,10,11,11a-hexahydro-5H-pyrrolo(2,1-c)(1,4)benzodiazepin-5,11-dione)
  • Antineoplastic Agents
  • Benzodiazepinones
  • Pyrroles