Journal Reading:

A comparison of weekly versus 3-weekly

cisplatin
during adjuvant radiotherapy for high-risk head
and neck cancer (HHNC)
Disusun Oleh:
Yeni Notanubun 102012435 UKRIDA
Fathinah Zuhudan R. 1102013107 YARSI
 ABSTRAK
To compare cumulative cisplatin dose & toxicity
between patients who:
OBJEKTIF received 3-weekly VS weekly cisplatin
during adjuvant radiotherapy for high-risk head &
neck squamous cell carcinoma (HNSCC)

HNSCC patients w/ involved resection margins

and/or extracapsular extension in 2 tertiary cancer
centers w/ different institutional practices
Calculated cumulative cisplatin dose & Information
METODE on toxicity reviewed
Compared between patients who received 3-weekly
VS weekly cisplatin
 ABSTRAK

270 high risk patients:

60 3-weekly 100 mg/m2
48 weekly 50 mg/m2 cisplatin during
adjuvant radiotherapy (6066 Gy in 3033
HASIL fractions).

Mean cumulative cisplatin dose:

199.4 mg/m2 (SE 5.4) in 3-weekly
239.8 mg/m2 (SE 11.0, P = 0.001) in weekly
 ABSTRAK

Cumulative cisplatin >200 mg/m2 was given to:

67.7% of patients in 3-weekly cohort
85.2% (P = 0.039) in the weekly cohort.
HASIL
The rate of feeding tube dependency 6 months
after treatment, osteoradionecrosis, neutropenic
fever, & persistent renal function decline were not
statistically different.
 ABSTRAK

Patients treated w/ weekly 50 mg/m2 cisplatin

received a higher cumulative dose w/ comparable
toxicity as patients who received 3-weekly 100
KESIMPULAN mg/m2 cisplatin.
Efficacy & applicability to the frequently used
weekly 40 mg/m2 schedule remains to be evaluated
PENDAHULUAN

Patients HNSCC treated w/

primary surgery
have a very high risk of The combination of adjuvant
recurrence radiotherapy & high dose
IF resection margins (+) &/ cisplatin
IF there is extra-capsular induces significant acute &
extension of lymph node long term toxicity [1,2].
metastases.
3 studies demonstrated
that these patients derive
benefit from adding high
dose cisplatin [13].
PENDAHULUAN

However, weekly
and 3- weekly As an alternative, a weekly lower
cisplatin plus dose cisplatin schedule has been
radiotherapy have used, based on the assumption that
not been compared a weekly regimen is less toxic and
directly in a equally effective as 3-weekly high
randomized and dose cisplatin
adequately
powered study
TUJUAN

Aimed to compare:
1. Patient cohorts from 2 tertiary care centers
where one center routinely treats high-risk HNSCC patients postoperatively
with 3-weekly high dose cisplatin
and the other center routinely gives weekly cisplatin.

If weekly cisplatin is better tolerated than 3-weekly cisplatin,

this might be reflected by a higher cumulative cisplatin dose in patients
treated with a weekly schedule.
2. The cumulative cisplatin dose & toxicity between patients treated with a
weekly schedule & patients treated with the high dose 3-weekly schedule.
METODE

Retrospective cohort study

All consecutive patients w/ HNSCC who underwent
primary surgery & had (+) resection margins (<1mm)
Study design, &/ extra-capsular extension of lymph node
patients, & metastasis
treatment
stared adjuvant radiotherapy 01/03/2005 12/12/12
at PM & 15/12/2008 15/07/2013 at UMCG
institutional database & patient rec.
METODE

PM 3 cycles of 3-weekly 100 mg/m2 cisplatin

UMCG 7 weekly cycles cisplatin 50 mg/m2
for both cisplatin schedules, patients were admitted
Study design, overnight for equivalent hydration regimens
patients, &
treatment
PM postoperative IMRT
UMCG IMRT w/ simultaneous integrated boost
technique
METODE

Patients received 66 Gy in 2Gy fractions on high risk

areas; 59,4 Gy in 1,8 Gy per fraction on intermediate
rsk areas; and 52,8 Gy on the elective nodal areas
Study design,
patients, &
treatment All patients treated with 3-weekly high-dose
&weekly cisplatin (if the caloric intake by mouth was
insufficient) underwent prophylactic percutaneous
endoscopic gastrostomy (PEG)
METODE

Primary endpoint: the cumulative cisplatin dose,

defined as the total dose in mg/m2 that a patient
received during the course of adjvant radiation
Secondary endpoints: included:
rate of tube feeding dependence at 6 months after
chemoradiotherapy;
Study endpoints
the rate of osteoradionecrosis of the jaw after
& data analyses
treatment;
the rate of neutropenic fever during treatment;
the worst change of serum creatinine according to
the common terminology criteria for adverse
events version 4.0 (CTCAE 4.0);
the change in body weight during treatment.
METODE

Compared using
Study endpoints two-sample t-tests
& data analyses chi-squared test or Fishers exact
Calculated using the binary logistic regression model
analyses were performed with SPSS version 19
 HASIL

Fourteen PM
patients were
excluded from the
cumulative dose
and toxicity
comparisons
because of
treatment with:
HASIL

The most
frequently
documented
reasons for
withholding
chemotherapy
 during High dose 50 mg/m2
HASIL adjuvant
radiotherapy.

Chemo-
Radiotherapy
Comparison Cohort
 HASIL
Chemo-
Radiotherapy
Comparison Cohort
 HASIL All patients were treated with
intensity modulated radiation
therapy (IMRT).
Chemo- All patients except for one in the
Radiotherapy 3-weekly cohort completed
Comparison Cohort radiotherapy.

Patients treated with 3-weekly

cisplatin received 6072 Gy in 30
36 fractions.
All except one patient in the
weekly cisplatin cohort received
66 Gy in 33 fractions
 HASIL The mean cumulative cisplatin dose was
Cumulative higher in patients treated with weekly
Cisplatin cisplatin (239.8 mg/m2 , standard error
Dose (SE) 11.0)
Also the percentage of patients who
received a cumulative cisplatin dose
>200 mg/m2 was higher in the weekly
cohort (85.2%)
There was no significant interaction
between RT dose schedule, cisplatin
regimen, and the cumulative mean
cisplatin dose (p = 0.34)
 Treatment The toxicity rates between patients
HASIL Morbidity
treated with the 3-weekly and
weekly regimens were similar

Of all weekly treated

patients, 40% completed
treatment without tube
feeding.

was low and not signifi-

cantly different between
treatment cohorts
 Treatment The cumulative cisplatin dose
HASIL Morbidity
was similar in patients with and
patients without
osteoradionecrosis
The baseline
creatinine value was
compared with the
highest creatinine
value between start &
6 weeks aft treatment
for each patient
no grade 4, only 1
grade 3 renal toxicity
in both
6 weeks aftr
completion of
treatment, grade 1
present in 2 patients
3-weekly cohort & 3
patients weekly
Only 1 patient 3-
weekly had
permanent grade 2
 HASIL
Recurrance
Rate
DISKUSI

weekly regimen allowed for

more cisplatin to be
delivered during radiation, patients treated with the weekly
without evidence of added regimen had more frequent and
toxicity more severe mucositis This trial
used a weekly 40 mg/m2 cisplatin
dose
DISKUSI
lower rate of feeding tube
use during treatment, weight
loss was less in patients
treated with weekly cisplatin
in our study.
feeding tube insertion was
performed in 90% of 3-weekly
treated patients and 41% of
weekly treated patients, but in
contrast to our results more
weekly treated patients
experienced P10% weight loss
KESIMPULAN

This retrospective comparison has demonstrated that

around one half of high-risk HNSCC patients are not eligible
for cisplatin during postoperative radiotherapy.
Weekly 50 mg/m2 cisplatin permits a higher cumulative
dose to be delivered with no evidence of excess toxicity
compared to 3-weekly 100 mg/m2 cisplatin during
postoperative radiotherapy.
Efficacy remains to be determined and it is unclear if this
data is applicable to the 40 mg/m2 weekly cisplatin
schedule, which is a commonly used alternative to high
dose 3-weekly cisplatin.6
TERIMAKASIH
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