Map at high doses: Positive and undesirable side-effects

203s

MAP

AT HIGH DOSES: ‘Pam-a&i,

*Oncology

POSITIVE

Division,

AND

S. Oraola-hf.

Malpighi

Since 1975, an lurociation activity

in metastatic

number

of side-effects

Cushing-like

Hospital,

between

can occur. The 7.7X,

gluteal

constipation

in local

thrombopblebitis

principal abscess

absorption

my

occur.

increase ia not yet known. During

a diabetogenic

acetate with chemotherapy

myelosuppreaaive of bone marrow

devoid

tremors

to the disturbance8

and vaginal

(oral

spotting

reported,

rarer

effects which can be useful in many patients, in 65% of patients

adjustment

Although

medication

in the incidence

of thin protection

agains leukopenia

(incidence

spotting

anorexia

lO.l%,

2% (oral

with an incidence

leas than

of

im.,

1%) are rashes,

10 to 20%). The reason for this

such 81) pain relief, weight

increase and leukocytosis,

of the objective

an3 a positive

known to have diabetes.

of leukopenia.

is not yet understood

haa been found. A dose-response

4%,

When the drug is administered

(mean incidence

intake

antitumor

response. Weight

nitrogen

balance. Some

have not been able to confirm this effect, it is possible that

in patient,

and severity

11.8%. vaginal

were most frequent,

activity.

side-effects

caloric

and significant

administration)

and wan independent

with increased

other investigators

of antidiabetic

allows a reduction

cell8 to daunorubicin

with bone metsstases

and is associated

Italy

at low doses, with increase in dose, a

12.1%. sweating

6.4%, nausea/vomiting

tremon,sweating

Bologna,

of toxicity

features and leg cramps reflect glucocorticoid

effect of treatment.

drugs. The mechanism progenitor

are M followa:

cramps

1.9%. Fine

effect of treatment

increased caloric intake could necessitate gesterone

&nerved

muxular

of Bologna,

acetate (more than 600 mg/day)

While this progeatin is practically

In addition

treatment,

to an antianorexic

authors have reported

University

madroxyprogesterone

A transient increase in blood pressure bea also been reported

Pain relief has been observed

increase is related

of Organic Chemistry,

side-effects

&Q%,

1.6% and insomnia

and hypertrichosia.

become evident.

‘Institute

the use of high-dose

around 10 to 12%. Other effects such aa Cushing-like difficulties

SIDE-EFFECTS

CM.

breast cancer haa been recognised.

features

administration),

UNDESIRABLE

A. and ‘Camaggi,

F., ‘Martoni,

relationship

Combination

It also allows administration but recently

of medroxyproof higher doses of

no direct effect ont he sensitivity

of some side-effects

such as cramps, tremor

and

gluteal abscess has been observed.

a M&ptectiveEffectof~

Acetate (WN) mcomMedq3ulqx1ietic

stenoellsudercytntmic

ew Kle&en~ U.R, wander H.-E., Sdneidw P., km P. ~~lagisch~logische~~sAltonaudBanhard-N3cht_InstiM,Hntup,~y Bone mat-w toxicityis the aost importantdose limitingfactor of any systeniccytostaticchemotherapy(CT). 0-iginatingfro1 clinicalbservations it axlId be st-cw,that steroid hormxlesex& sore protectiw effect and that testosterone,gluowrticoids, and estrogenstamper grwlo- wd thrwixxytopenia,slot-ten the supct-ession of the prcgenitu-cells and irct-ease tt-erecoveryfollowingCT. In a prospectiveclinicaltrialcomparingthe effectsof Rqesttol acetate(WI) with high dose+MroqXogesterone Acetate (HI-WA) in patientswith disseminatedbreast cancer,w havs show, that both agents lead to a significant ircreasein hsmoglcbin,grwulccytes and platelets.Also a nmber of clinical studieshave been Mlished, suggestingdecreasedbone narrow toxicity,lzhenhigh doses of WA are added to cytotoxicagents. To define the actionof CPA on the haenatqoiesis and to exclude that the observedelevatedbloodcountsmerely reflect a shift fran the rrarginal into tte circulatingpool, as it is known fron glucccorticoids, w designeda prospectivecontrolledstudy: 24 patientswith progressivedisseminatedbreast cancer,ti had never been treated with CT before,vere randonlyassigwd to one group given FAC alone (5 FU: 500 mg/m' dlt3, ADM 500 q/m' dl, CPA 5oOq/mz dl i.v., q%v)or with additionalHDWA (1ooOng per 05 per day, beginningat least 1 week prior to treatirentand given througtolfthe CT-cowses). Besidescooltingthe perip+-eral blood cells v.eneasu-edtte granulccytenonccytecolony-fuming units &M-CFC), the prewred grivlulopoietic precursorsof the aomitted stercellcqartnent at wekly intervalsp-iu- to ard following 3 causes of CT. thder HO-LPA-treatrent there is a significant reductionin grwth wd absolutentier of GWFC as cqared to those patients,receivingFAC-CT only. CW results suggest,that WA in high doses inhibitsmitotic activityand differentiation of pluripotentprecursors into the ClJlGttKl starrcell ccmipartint,therebysaving the proliferatinggranulcpoietic progenitorcells fron the cytocidalactionof cytostaticagents. 9 TOXICITY MYCIN BREAST

ANALYSIS AND

OF

5-FLUORaTRACIL

A

MLJLTICENTER PLUS

OR

STUDY MINUS

OF

HIGH

ADJUVANT DOSE

m?@lENT

WITH

CYWPHOSPHAMIDE,

MEDROXYPRCGESTJZRONACNACFTATE

(MF’A)

ADRIAIN

EARLY

CANCER. Wils J., Blijham GB., Schouten L. Laurentiushospital,Rcermnd, State University Maastricht and Canprehensive Cancer Center Limburg, Maastricht, The Netherlands. In a randomized multicenter study conducted by 9 institutions, 360 patients (pts) with stage II-III breast cancer, all with positive axillary nodes, were treated with cyclophosphamide 500 mg/sqm,iv,doxorubicin40 rrg/sqm,iv, and 5-fluorouracil 500 mg/sqm,iv,all on day 1, to be repeated q 4 weeks, with or without high dose MPA 600 mg daily, orally days l-14,500 mg daily, im, day l-28, twice weekly thereafter. Treatment was continued for 6 months. Fourteen percent of pts had unknown ER-status. Pts with tumors <3cm had the choice between lmpectmy with axillary dissection or standard amputation. Radiotherapy to the breast was given to pts with a lumpectomy. WBO grade 3 nausea/vmiting occurred in 40% of pts in the combined arm vs 65% in the chemotherapy arm and hematolcgical grade 3 toxicity in 18% vs 29%. Considering all cycles the WBC oount nadirs were significantly higher in the combined treatment am. Dose reductions or postponement of treatment occurred in 4% in the combined arm and 9% in the chemotherapy arm. In 18% of pts MPA was discontinued after a median of 3 months for drug attributed toxicity reasons, mainly weight gain. For all pts the mean weight gain during treatment with high dose MPA was 6 kg. There has been no grade 4 toxicity and no clinical cardiotoxicity. After a median follm-up of 2 years the relapse rate was 23%. Ionger follow-up is necessary before a difference between both treatment arms or between subsets (ER+/ER-; pre-/postmenopausal)can be assessed. In conclusion this study shms that anthracycline containing adjuvant chemotherapy produces moderate side effects which are attenuated by concomitant use of high dose MPA. Supported by Farmitalia Carlo Erba.