AUTHOR=Kinsella Timothy J., Baron Elma , Colussi Valdir , Cooper Kevin , Hoppel Charles , Ingalls Stephen , Kenney Malcolm , Li Xiaolin , Oleinick Nancy , Stevens Seth , Remick Scot TITLE=Preliminary Clinical and Pharmacologic Investigation of Photodynamic Therapy with the Silicon Phthalocyanine Photosensitizer Pc 4 for Primary or Metastatic Cutaneous Cancers JOURNAL=Frontiers in Oncology VOLUME=1 YEAR=2011 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2011.00014 DOI=10.3389/fonc.2011.00014 ISSN=2234-943X ABSTRACT=

Photodynamic therapy (PDT) for cutaneous malignancies has been found to be an effective treatment with a range of photosensitizers. The phthalocyanine Pc 4 was developed initially for PDT of primary or metastatic cancers in the skin. A Phase I trial was initiated to evaluate the safety and pharmacokinetic profiles of systemically administered Pc 4 followed by red light (Pc 4-PDT) in cutaneous malignancies. A dose-escalation study of Pc 4 (starting dose 0.135 mg/m2) at a fixed light fluence (135 J/cm2 of 675-nm light) was initiated in patients with primary or metastatic cutaneous malignancies with the aim of establishing the maximum tolerated dose (MTD). Blood samples were taken at intervals over the first 60 h post-PDT for pharmacokinetic analysis, and patients were evaluated for toxicity and tumor response. A total of three patients (two females with breast cancer and one male with cutaneous T-cell lymphoma) were enrolled and treated over the dose range of 0.135 mg/m2 (first dose level) to 0.54 mg/m2 (third dose level). Grade 3 erythema within the photoirradiated area was induced in patient 2, and transient tumor regression in patient 3, in spite of the low photosensitizer doses. Pharmacokinetic observations fit a three-compartment exponential elimination model with an initial rapid distribution phase (∼0.2 h) and relatively long terminal elimination phase (∼28 h), Because of restrictive exclusion criteria and resultant poor accrual, the trial was closed before MTD could be reached. While the limited accrual to this initial Phase I study did not establish the MTD nor establish a complete pharmacokinetic and safety profile of intravenous Pc 4-PDT, these preliminary data support further Phase I testing of this new photosensitizer.