PMID- 20623160
OWN - NLM
STAT- MEDLINE
DCOM- 20120123
LR  - 20211203
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Linking)
VI  - 29
IP  - 6
DP  - 2011 Dec
TI  - Phase I study of weekly plitidepsin as 1-hour infusion combined with carboplatin 
      in patients with advanced solid tumors or lymphomas.
PG  - 1406-13
LID - 10.1007/s10637-010-9488-1 [doi]
AB  - This dose-escalating phase I clinical trial was designed to determine the 
      recommended dose (RD) and to assess the safety and feasibility of weekly 
      plitidepsin (1-hour i.v. infusion, Days 1, 8 and 15) combined with carboplatin 
      (1-hour i.v. infusion, Day 1, after plitidepsin) in 4-week (q4wk) cycles given to 
      patients with advanced solid tumors or lymphomas. Twenty patients were enrolled 
      and evaluable for both safety and efficacy. The starting dose was plitidepsin 1.8 
      mg/m(2) and carboplatin area under the curve (AUC) = 5 min*mg/ml; dose escalation 
      proceeded based on worst toxicity in the previous cohort. The maximum tolerated 
      dose (MTD) was plitidepsin 3.0 mg/m(2) and carboplatin AUC = 5 min*mg/ml, with 
      grade 3 transaminase increases as the most common dose-limiting toxicities 
      (DLTs). The RD for phase II studies was plitidepsin 2.4 mg/m(2) and carboplatin 
      AUC = 5 min*mg/ml, with fatigue, myalgia and nausea as the most common 
      drug-related adverse events (AEs). No unexpected toxicity was seen. Twelve 
      patients (60%), ten of whom were heavily pretreated (>/=2 previous chemotherapy 
      lines) showed stable disease (SD), with a median time to progression (TTP) of 4.4 
      months. In conclusion, plitidepsin 2.4 mg/m(2) and carboplatin AUC = 5 min*mg/ml 
      is a safe dose for future phase II studies evaluating the use of this combination 
      in cancer patients potentially sensitive to platinum-based therapy.
FAU - Salazar, Ramon
AU  - Salazar R
AD  - Instituto Catalan de Oncologia, Ctra. Gran Via, s/n, L'Hospitalet de Llobregat, 
      08907, Barcelona, Spain. ramonsalazar@iconcologia.net
FAU - Plummer, Ruth
AU  - Plummer R
FAU - Oaknin, Ana
AU  - Oaknin A
FAU - Robinson, Angela
AU  - Robinson A
FAU - Pardo, Beatriz
AU  - Pardo B
FAU - Soto-Matos, Arturo
AU  - Soto-Matos A
FAU - Yovine, Alejandro
AU  - Yovine A
FAU - Szyldergemajn, Sergio
AU  - Szyldergemajn S
FAU - Calvert, Alan Hilary
AU  - Calvert AH
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20100710
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Depsipeptides)
RN  - 0 (Peptides, Cyclic)
RN  - BG3F62OND5 (Carboplatin)
RN  - Y76ID234HW (plitidepsin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse 
      effects/*therapeutic use
MH  - Area Under Curve
MH  - Carboplatin/administration & dosage
MH  - Depsipeptides/administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Infusions, Intravenous
MH  - Lymphoma/*drug therapy/pathology
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasms/*drug therapy/pathology
MH  - Peptides, Cyclic
MH  - Treatment Outcome
EDAT- 2010/07/14 06:00
MHDA- 2012/01/24 06:00
CRDT- 2010/07/13 06:00
PHST- 2010/05/26 00:00 [received]
PHST- 2010/06/24 00:00 [accepted]
PHST- 2010/07/13 06:00 [entrez]
PHST- 2010/07/14 06:00 [pubmed]
PHST- 2012/01/24 06:00 [medline]
AID - 10.1007/s10637-010-9488-1 [doi]
PST - ppublish
SO  - Invest New Drugs. 2011 Dec;29(6):1406-13. doi: 10.1007/s10637-010-9488-1. Epub 
      2010 Jul 10.