Table 2. Toxicities, treatment, genotype, and PK analysis.
|
Patient A
|
Patient B
|
Patient C
|
||||
|---|---|---|---|---|---|---|
| Grade | Value | Grade | Value | Grade | Value | |
| Haematologic toxicities a | ||||||
| Leukocyte (mm−3) | 4 | 800 | 3 | 1100 | 3 | 1000 |
| Neutrophil (mm−3) | 4 | 200 | 4 | 300 | 4 | 100 |
| Haemoglobin (g dl−1) | 2 | 8.1 | 1 | 13.2 | 4 | 6.3 |
| Platelet (mm−3) | 3 | 26 000 | 4 | 10 000 | 3 | 28 000 |
| Non-haematologic toxicity a | ||||||
| Fatigue | 2 | 3 | 2 | |||
| Anorexia | 3 | 3 | 2 | |||
| Diarrhoea | 3 | 0 | 1 | |||
| Stomatitis | 3 | 0 | 0 | |||
| Rash | 2 | 0 | 2 | |||
| Febrile neutropaenia | 3 | 0 | 0 | |||
| Treatment | ||||||
| Resumption of chemotherapy | Yes | No | Yes | |||
| Total number of gemcitabine doses | 10 | 2 | 10 | |||
| Final dose (mg m−2) | 600 | 1000 | 270 | |||
| Genotype | ||||||
| CDA haplotypeb | *1a/*1j | *3a/*3a | *3a/*3a | |||
| DCK haplotypec | *1a/*1a | *1a/*1a | *1a/*1a | |||
| PK analysis | ||||||
| Regimen at PK study | Gemcitabine alone | Gemcitabine alone | ||||
| Dose of gemcitabine (mg m−2) | 1000 | 450 | ||||
| Cmax (mg l−1) | 29.0 | Not available | 22.5 (49.7d) | |||
| AUC (mg h l−1) | 16.2 | 26.8 (59.0d) | ||||
| Clearance (l h−1 m−2) | 61.8 | 16.6 | ||||
AUC=area under the concentration–time curve; Cmax=maximum plasma concentration; CDA=cytidine deaminase; DCK=deoxycytidine kinase; PK=pharmacokinetics.
a
Toxicities were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.
b
CDA haplotype was reported earlier in Sugiyama et al (2007).
c
DCA haplotype was reported earlier in Kim et al (2008).
d
On the basis of the assumption that patient C received 1000 mg m−2 of gemcitabine.