PMID- 17699865
OWN - NLM
STAT- MEDLINE
DCOM- 20070925
LR  - 20131121
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 13
IP  - 16
DP  - 2007 Aug 15
TI  - Phase I and pharmacokinetic study of the (6-maleimidocaproyl)hydrazone derivative 
      of doxorubicin.
PG  - 4858-66
AB  - PURPOSE: The (6-maleimidocaproyl)hydrazone derivative of doxorubicin (DOXO-EMCH) 
      is an albumin-binding prodrug of doxorubicin with acid-sensitive properties that 
      shows superior antitumor efficacy in murine tumor models and a favorable toxicity 
      profile in mice, rats, and dogs compared with doxorubicin. The purpose of the 
      phase I study was to characterize the toxicity profile of DOXO-EMCH, establish a 
      recommended dose for phase II studies, and assess potential anticancer activity. 
      EXPERIMENTAL DESIGN: A starting dose of 20 mg/m2 doxorubicin equivalents was 
      chosen. Forty-one patients with advanced cancer disease were treated with an i.v. 
      infusion of DOXO-EMCH once every 3 weeks at a dose level of 20 to 340 mg/m2 
      doxorubicin equivalents. RESULTS: Treatment with DOXO-EMCH was well tolerated up 
      to 200 mg/m2 without manifestation of drug-related side effects. Myelosuppression 
      (grade 1-2) and mucositis (grade 1-2) were the predominant adverse effects at 
      dose levels of 260 mg/m2 and myelosuppression (grade 1-3) as well as mucositis 
      (grade 1-3) were dose limiting at 340 mg/m2. No cardiac toxicity was observed. Of 
      30 of 41 evaluable patients, 12 patients (40%) had progressive disease, 15 
      patients (57%) had stable disease, and 3 patients (10%) had a partial remission. 
      CONCLUSIONS: DOXO-EMCH showed a good safety profile and was able to induce tumor 
      regressions in tumor types known to be anthracycline-sensitive tumors, such as 
      breast cancer, small cell lung cancer, and sarcoma. The recommended doxorubicin 
      equivalent dose for phase II studies is 260 mg/m2.
FAU - Unger, Clemens
AU  - Unger C
AD  - Department Medical Oncology, Tumor Biology Center, Freiburg, Germany. 
      unger@tumorbio.uni-freiburg.de
FAU - Haring, Brigitte
AU  - Haring B
FAU - Medinger, Michael
AU  - Medinger M
FAU - Drevs, Joachim
AU  - Drevs J
FAU - Steinbild, Simone
AU  - Steinbild S
FAU - Kratz, Felix
AU  - Kratz F
FAU - Mross, Klaus
AU  - Mross K
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Hydrazones)
RN  - 0 (Prodrugs)
RN  - 151038-96-9 (doxorubicin(6-maleimidocaproyl)hydrazone)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibiotics, Antineoplastic/*adverse effects/pharmacokinetics
MH  - Doxorubicin/adverse effects/*analogs & derivatives/pharmacokinetics
MH  - Female
MH  - Heart/drug effects
MH  - Humans
MH  - Hydrazones/*adverse effects/pharmacokinetics
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasms/*drug therapy
MH  - Prodrugs/*adverse effects/pharmacokinetics
MH  - Skin/drug effects
EDAT- 2007/08/19 09:00
MHDA- 2007/09/26 09:00
CRDT- 2007/08/19 09:00
PHST- 2007/08/19 09:00 [pubmed]
PHST- 2007/09/26 09:00 [medline]
PHST- 2007/08/19 09:00 [entrez]
AID - 13/16/4858 [pii]
AID - 10.1158/1078-0432.CCR-06-2776 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2007 Aug 15;13(16):4858-66. doi: 10.1158/1078-0432.CCR-06-2776.