A search of the literature did not find strong evidence to support the use of gemcitabine in the treatment of recurrent or metastatic nasopharyngeal cancer. The expert reference panel supported publication of the protocol on the basis of the information summarised below. The committee was most strongly influenced by two phase 2 studies demonstrating reasonable response rates in patients following previous chemotherapy with minimal significant toxicity.
Between January and November 1999, a total of 52 patients with metastatic nasopharyngeal carcinoma were treated with single agent gemcitabine at a dose of 1250mg/m2. Patients were recruited into two parallel phase 2 studies; in group 1, 25 patients were chemotherapy naive while the 27 in group 2 had previously received chemotherapy.r
A small study of 32 patients with advanced (stage IV) or metastatic nasopharyngeal carcinoma who had previously received platinum based chemotherapy were treated with single agent gemcitabine at a dose of 1000 mg/m2 on day 1, 8, 15 of a 28 day cycle as part of a single arm phase 2 trial.r
In a retrospective review of patients treated between January 2000 and October 2001 at the Princess Margaret Hospital in Toronto, 18 patients with inoperable locally advanced disease not amenable to radiation therapy or metastatic disease were found to have received single agent gemcitabine at a dose of 1000 mg/m2 on day 1,8,15 of a 28 day cycle.r
Source |
Study & Year Published |
Supports Use |
Is the dose and regimen consistent with the protocol? |
Comments |
Phase II trials |
Foo et al 2002r |
Yes |
1250 mg/m2 Day 1,8 3 weekly |
Prior chemotherapy regimens included 5FU+cisplatin; single agent cisplatin; oral 5FU+eniluracil; paclitaxel+carboplatin
|
|
Zhang et al 2007r |
Yes |
Yes |
Prior chemotherapy regimens included 5FU+cisplatin; cisplatin+capecitabine; carboplatin+paclitaxel
|
Case series |
Ma et al 2002r |
Yes |
Yes |
Prior chemotherapy regimens included cisplatin, doxorubicin, methotrexate, bleomycin, and cyclophosphamide; cisplatin+5FU or docetaxel
|
Observational studies |
- |
N/A |
- |
|
Guidelines |
Date published/revised |
Supports Use |
Is the dose and regimen consistent with the protocol? |
Comments |
NCCN |
version 1. 2012 |
Yes |
no dose |
|
BCCA |
Nov 2012 |
Yes |
no |
1250 mg/m2 days 1, 8 3 weekly |
CCO |
- |
N/A |
- |
|
Efficacy
Gemcitabine was evaluated in two groups of patients.r
Trial 1: first line therapy for chemo-naive patients.
Trial 2: salvage treatment in patients who have failed or progressed after treatment with other chemotherapy agents.
Median time to progression and overall survival were 3.6 and 7.2 months respectively for the patients in group 1; while for the patients in group 2 median time to progression and overall survival were 5.1 and 10.5 months respectively.
Responser |
Number of patients = 25
(%) |
Trial 1 |
Complete response |
4 |
Partial response |
24 |
Stable disease |
28 |
Progression |
28 |
Unable to evaluate |
16 |
Overall response rate |
28% (14.3-47.6) 95% CI |
Responser |
Number of patients = 27
(%) |
Trial 2 |
Complete response |
4 |
Partial response |
44 |
Stable disease |
30 |
Progression |
11 |
Unable to be evaluated |
11 |
Overall response rate |
48% (30.7-66.0) 95%CI |
Zhang et al studyr
Median time to progression and overall survival were 5.1 months and 16 months respectively
Responser |
Number of patients = 32
(%)
|
Complete response |
0 |
Partial response |
43.8 (95% CI 26.6-61.0%) |
Stable disease |
28.1 |
Progression |
21.9 |
Unable to evaluate |
6.3 |
Overall response |
44 |
Ma et alr
Median progression free survival was 20 weeks, and median overall survival was not reported at the time of publication.
Responser |
Number of patients = 18 (%)
|
Complete response |
6 |
Partial response |
28 |
Stable disease |
22 |
Progression |
22 |
Unable to evaluate |
22 |
Overall response |
34 |
Toxicity
Toxicityr |
Trial 1 |
Grade 3 |
Grade 4 |
Patient
n=25
(%) |
Cycle
n=102
(%) |
Patient
n=25
(%) |
Cycle
n=102
(%) |
Anaemia |
32 |
13 |
4 |
1 |
Alkaline phosphatase |
16 |
4 |
0 |
0 |
Neutropenia |
4 |
1 |
0 |
0 |
Leukopenia |
4 |
1 |
0 |
0 |
Thrombocytopenia |
8 |
3 |
0 |
0 |
Infection |
4 |
1 |
4 |
1 |
Neurotoxicity |
8 |
3 |
0 |
0 |
Other* |
4 |
1 |
0 |
0 |
*Other includes nausea and vomiting
Toxicityr |
Trial 2 (prior chemotherapy) |
Grade 3 |
Grade 4 |
Patient
n=27
(%) |
Cycle
n=135
(%) |
Patient
n=27
(%) |
Cycle
n=135
(%) |
Anaemia |
15 |
5 |
4 |
1 |
Alkaline phosphatase |
7 |
4 |
4 |
1 |
Neutropenia |
37 |
11 |
0 |
0 |
Leukopenia |
18 |
4 |
0 |
0 |
Thrombocytopenia |
0 |
0 |
4 |
1 |
Infection |
0 |
0 |
0 |
0 |
Neurotoxicity |
0 |
0 |
0 |
0 |
Other* |
4 |
1 |
0 |
0 |
*Other includes transaminitis
In the Zhang et alr study minimal toxicities were reported. Most notably, grade 3/4 neutropenia was experienced by 15.6% and 3.1% of patients respectively. 3.1% of patients experienced grade 3 anaemia and thrombocytopenia. The only other toxicity grade 3/4 toxicity reported was transaminitis in 6.3 and 3.1 % respectively.
Ma et alr reported gemcitabine to be well tolerated and haematological toxicities were those most frequently reported. 39% of patients experienced grade 3 neutropenia and 11% had grade 3 thrombocytopenia, 5% had grade 4 thrombocytopenia.