TREATMENT OF MALIGNANT PLEURAL EFFUSIONS

Project: Research project

Project Details

Description

Multilamellar liposomes administered into body cavities tend to remain
for a prolonged period of time inside the cavity and are mainly drained
by the lymphatic system. This may enhance the therapeutic effects of
drugs incorporated in liposomes inside the cavity and in the regional
lymph nodes. L-NDDP is a lipophilic cisplatin analogue which has been
incorporated in multilamellar liposomes for its administration in humans.
L-NDDP is not cross-resistant with cisplatin in several in vitro and in
vivo systems. In a Phase I study in humans by intravenous
administration, L-NDDP was well tolerated and non-nephrotoxic. The dose
limiting toxicity was myelosuppression. The easy access to the pleural
cavity of patients with malignant pleural effusions provides a unique
opportunity for testing the pharmacological effects of cytotoxic agents
against human tumor cells ex vivo. We propose to conduct a Phase I-II
clinical study of L-NDDP by intrapleural administration in patients with
malignant pleural effusions. The objectives of the study are: 1) to
determine the maximum tolerated dose, spectrum of toxicity, and antitumor
efficacy of L-NDDP administered into the pleural space in patients with
malignant pleural effusions, 2) to correlate tumor response with Pt and
Pt-DNA levels in malignant cells from the pleural cavity and peripheral
leukocytes after the administration of L-NDDP into the pleural space, 3)
to study the pharmacokinetics of L-NDDP in plasma and pleural fluid, and
4) to determine the fate of multilamellar liposomes by nuclear imaging
techniques after the administration of 99mTc labeled liposomes into the
pleural space. The results of the study will indicate 1) the potential
of L-NDDP and other liposome-entrapped antitumor agents in the treatment
of malignant pleural effusions, and 2) the ability of liposomes infused
into the pleural cavity to target the mediastinal lymph nodes. If
significant mediastinal lymph node targeting is observed, agents such as
L-NDDP may be particularly useful as a therapeutic tool for the treatment
of mediastinal lymph node metastases, which are one the first sites of
dissemination of lung tumors.
StatusFinished
Effective start/end date9/30/929/29/93

Funding

  • National Cancer Institute

ASJC

  • Drug Discovery
  • Pulmonary and Respiratory Medicine
  • Toxicology
  • Pharmacology
  • Pharmaceutical Science

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