Document 138374

with oesophago-gastric cancer. The study was designed to
detect an improvement in response rates from 35% to 50%
with 170 patients per arm providing at least 80% power (a
error = 5%). The number of patients with colorectal cancer
randomised was increased to 100 per arm to ensure adequate
power as a separate study. We observed a significant improvement in response rate from 38% with protracted venous infusion (PVI) 5-fluorouracil (5-FU) alone to 54% with PVI 5-FU
plus mitomycin-C (P = 0.024). Due to haemolytic uraemic
syndrome associated with a cumulative mitomycin-C dose of
40 mg/m2 (10 mg/m2 per course) the cumulative dose of
mitomycin-C was reduced to 28 mg/m2 (7 mg/ m2 per course).
The 53 patients treated with the higher dose of mitomycin-C
had a response rate of 61% compared to 45% for the 45
patients treated at the lower dose. This difference was not
statistically significant. Further subgroup analysis was not
performed as the study was not designed to have enough
power to be analysed in such a way. After the mitomycin-C
dose was reduced, careful surveillance for evidence of haemolysis was instituted and no further mitomycin-C given if haemolysis was observed. Although we reduced the dose of mitomycin-C, the higher dose of mitomycin-C may still be safely
used if increased monitoring is instituted, but this needs to be
investigated further. Mitomycin-C in combination with PVI
5-FU significantly improves response and failure-free survival
but the optimal dose of mitomycin-C with respect to efficacy
In their paper published in Annals of Oncology [1], Ross et al. and toxicity requires clarification.
describe an advantage of the combination of mitomycin-C and
protracted venous infusion (PVI) of 5-fluorouracil as comP. Ross, A. Norman & D. Cunningham
pared to PVI-5-fluorouracil alone in the treatment of advanced
of Medicine, The Royal Marsden Hospital,
colorectal cancer. From the data presented, their conclusion is
inadequate for the following reasons:
Because of mitomycin-C associated toxicities, the dose of
mitomycin-C has been reduced from 10 mg/m2 to 7 mg/m2 in
June 1995. Although I could not find the exact number of
patients treated with the lower dose or the higher dose, it
appears that about half of the patients in this treatment arm
received the lower dose. Response rate in patients receiving
toe nails
higher dose of mitomycin-C was higher (61%) than the response We report two cases of onycholysis of the finger and
rate of patients receiving lower dose (55%). Due to the toxic- following the application of docetaxel (100 mg/m ) given as
ities seen, authors recommend treatment with the lower dose single agent chemotherapy for metastatic breast cancer.
A 69-year-old female patient underwent lumpectomy and
of mitomycin-C. However, their conclusion regarding the effect
lymph node dissection in October 1996. Histologic
of treatment includes data from patients having received higher
dose. Therefore, it can not be concluded that 5-FU and mito- examination revealed breast cancer (ductal, NOS type, pTlc,
G2) with two out of 14 lymph nodes positive. The patient
mycin-C at lower dose is superior to 5-FU alone.
received three cycles of a CMF therapy regimen postoperatively. In March 1997 the CMF therapy was interrupted, beR. Herrmann
cause liver ultrasound and X-ray examination revealed multiple
Division of Oncology, Kantonsspital, 4031 Basel, Switzer-metastases in the liver, spine, and osseous pelvis. Instead, a high
dose adriamycin (100 mg/m2)-cyclophosphamide (600 mg/m2)
combination chemotherapy was given over two cycles. Due to
severe leukopenia, the chemotherapy regimen was changed
again and docetaxel (100 mg/m2) was given in April 1997. A
dose of 171 mg was administered over a one-hour infusion for
1. Ross P, Norman A, Cunningham D et al. A prospective rando- three cycles every three weeks.
mised trial of protracted venous infusion 5-fluorouracil with or
A 73-year-old female patient received neoadjuvant CMF
without mitomycin C in advanced colorectal cancer. Ann Oncol
for inflammatory breast cancer. After three
1997; 8 (10): 995-1001.
cycles of treatment, radical mastectomy with axillary node
dissection was performed in December 1996. Histologic examination revealed multicentric breast cancer (ductal, pT2,
This letter was referred to the authors who
G2) with seven out of 16 lymph nodes positive. The patient
three cycles of a combination chemotherapy, containrespond as follows:
ing 5-fluouracil (1000 mg), cyclophosphamide (800 mg), and
mitozantrone (10 mg/m2), at four-week intervals. During this
The study which we reported in the October 1997 edition of
Annals of Oncology was designed as part of a stratified study treatment the patient developed multiple metastases in the liver
2. Lambert HE, Rustin GJS, Gregory WM, Nelstrop AE. A randomized trial offiveversus eight courses of cisplatin or carboplatin in
advanced epithelial ovarian cancer: A North Thames Ovary Group
Study. Ann Oncol 1997; 8: 327-33.
3. Colombo N, Maggioni A, Coleoni R et al. Surgery for advanced
ovarian cancer. Proceedings of Perugia international cancer conference II on recent advances in treatment of testicular and ovarian
cancer 1989.
4. Bruzzone M, Repetto L, Chiara S et al. Chemotherapy versus
radiotherapy in the management of ovarian cancer patients with
pathological complete response or minimal residual disease at
second look. Gynecol Oncol 1990; 38: 392-5.
5. Krafft W, Glaser FH,Wenzel U et al. Moglichkeiten zur Erhaltung
der kompletten Remission beim zytoststich behandelten Ovarialkarzinom. In Meerpohl HG, Pfleiderer A, Profous CZ (eds): Das
Ovarialkarzinom. Berlin/Heidelberg/New York: Springer-Verlag
1993: 137^0.
6. Advanced Ovarian Trialists Group. Chemotherapy in advanced
ovarian cancer: An overview of randomised clinical trials. BMJ
1991; 303: 884-93.
Onycholysis in patients treated with
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5-Fluorouracil and mitomycin-C in
colorectal cancer: Unacceptable
A. Obermair, M. Binder, M. Barrada, D. BancherTodesca, E. Asseryanis & E. Kubista
University Hospital Medical School Vienna, A-1090
Vienna, Austria
1. Curran CF. Onycholysis in doxorubicin-treated patients. Arch
Dermatol 1990; 126: 1244 (Letter).
2. Creamer JD, Mortimer PS, Powles TJ. Mitozantrone-induced onycholysis. A series offivecases. Clin Exp Dermatol 1995; 20:459-61.
3. Obermair A, Vavra N, Kurz C et al. Onycholysis of the finger and
toenails following the application of high-dose oral etoposide (1250
mg/m2) given as 200- and 150-mg single doses from days 1-10
every three weeks. Gynecol Oncol 1995; 57: 436 (Letter).
4. Trudeau ME. Docetaxol (Taxotere): An overview of first-line
monotherapy. Semin Oncol 1995; 22: 17-21.
5. Slee PHTJ. Nail changes after chemotherapy. N Engl J Med 1997;
337:168 (Case report).
Quality of life assessment in patients
receiving adjuvant therapy for breast
cancer: The IBCSG approach
Figure 1 of the recently published paper [1] is labeled incorrectly. The labeling of the lines is reversed. The information in
the text, however, is correct: quality of life scores at time points
when patients were assigned to receive CMF therapy were
systematically lower compared to timepoints without assigned
chemotherapy, although the difference diminished over time.
We apologize for this error. The figure will be corrected on all
reprints which are available by the undersigned. The corrected
figure is printed herewith.
J. Bernhard
IBCSG Coordinating Center, 3008 Bern, Switzerland
C,D ^
50 , —1
1 1 —1
1 1 H
K 1
1 1
Figure 1. Median PACIS scores in trial VII (postmenopausal nodepositive patients) at time points where patients received chemotherapy.
Groups are combined according to whether or not the patients were
receiving chemotherapy at a given time point. All patients also received
Tamoxifen. Higher scores indicate better adjustment, /"-values are
from ANOVA's at each time point using 100 minus square root of
PACIS, controlling for culture and excluding patients who recurred
within the first 18.5 months. A, B, C, D refer to treatment groups (see
text for description).
1. Bernhard J, Hiirny C, Coates AS et al. for the International Breast
Cancer Study Group (IBCSG). Quality of life assessment in patients receiving adjuvant therapy for breast cancer: The IBCSG
approach. Ann Oncol 1997; 8: 825-35.
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and in the skin of the left arm. Therefore, in May 1997 she was
given docetaxel as first line chemotherapy for metastatic breast
cancer. A dose of 169 mg was administered over a one-hour
infusion for two cycles every three weeks.
Both patients developed burning pain, hyperaemia, and
appreciable epidermolysis between the fingers and the toes
after two cycles of treatment. While the first patient continued
docetaxel treatment, the second discontinued the therapy. After
three cycles of docetaxel the first patient presented with multiple and bilateral onycholysis of the finger and toe nails with
brown discoloration as a sign of bleeding beneath the nails.
The second patient presented with so-called Beau-Reil lines,
indicating that nail growth had stopped due to chemotherapy.
Additionally, beginning onycholysis was observed at the basal
layer of multiple finger and toe nails. In both patients a dermatological examination showed no evidence of infectious origin
of the alterations.
To date, only a few case reports and letters have been
published on the developent of onycholysis associated with
anthracyclines [1], mitozantrone [2] and etoposide [3]. After
using docetaxel as first-line chemotherapy in the treatment of
metastatic breast cancer, nail disorders, including ridging,
pain, and onycholysis were reported to occur in 35% of the
patients but rarely to be severe [4]. Recently, Slee reported a
case of nail changes following seven courses of docetaxel at
three-week intervals [5]. Although both of our patients had
undergone previous treatment with anthracyclines and mitozantrone, the clinical course clearly showed that the nail
changes were related to docetaxel. We therefore suggest that
investigators should pay special attention to this uncommon
side effect, in particular to the frequency of docetaxel-related