Drug Metabolism in Drug Design and Development Basic Concepts and Practice

(nextflipdebug2) #1
TABLE 6.2 Outcome of some of the Phase III clinical trials with ABC transporter inhibitors.Year

Trialgroup

Number of
patients

Cancer type

Modulator Anticancer drugs

Outcome

Reference

1995 MRC

235

Relapsed andrefractory AML

Cyclosporin Daunorubicin

CytarabineEtoposide

No benefit

Yin et al. (2001)

1998 SWOG

226

Poor-risk AML,

RAEB-t

Cyclosporin Daunorubicin

Cytarabine

Improved OS in
P-gp positive

patients

List et al. (2001)

1996 Novartis

256

AML

PSC833

DaunorubicinCytarabineEtoposide

No benefit

Sonneveld et al. (2001)

2000 CALGB

410

Untreated AML

PSC-833 Daunorubicin

EtoposideCytarabine

No OS advantage forthose

>

45 years; OS

benefit for those

<

45 years

Baer et al. (2002)

1996

315

Poor-risk acute

leukemia

Quinine

Mitoxantrone

Cytarabine

No benefit

Solary et al. (1996)

1996 GFM

131

High risk MDS

Quinine

Mitoxantrone

Cytarabine

Improved OS in
P-gp positive patients

Wattel et al. (1999)

1999 GEO-

LAMS

425

De novo

AML

Quinine

IdarubicineCytarabineMitoxantrone

Significant improvementin the CR rate in P-gp

positive patients.No OS advantage

Solary et al. (2003)

AML, acute myelogenous leukemia; CR, complete response; MDS, myelodysplastic syndrome; OS, overall survival; RAEB-t, refractory anemia with exce

ss of

blasts in transformation; RR, response rate.

156

Free download pdf