Carboplatin and etoposide in advanced lung cancer: — A phase I study

273

pears to have moderate cancer, the addition vinblastine

antitumor

activity

of ifosfamtde

against non-small-cell

to the combmatton

did not seem to improve

lung

of cisplatin

and

the response rate.

were compared.

At 30 min after the beginning

blood samples and bronchoscopically taken

for determinations

of platinum

flameless atomic absorption

High-dose cisplatin and mitomycin C in advanced non-small cell lung cancer: A phase II study of the Northern California Oncology Group Gandara

DR,

Perez EA.

Wold

H, Caggiano

al.l/niversiryofCaliforniaService. Marrinez.

CA 94553.

To investigate small-cell

VAMedicalCenter.

Cancer Chemother

chemotherapeutic

lung cancer (NSCLC),

destgned schedule of high-dose plus mitomycin

V, Malec

C. Between

Pharmacol

we evaluated

March

non-

1987 and March

28&y

cycle)

1989.62

patients

were registered for

a phase II study ofthe Northern CalifomtaOncology

Group

The

(NCOG).

hypertonic

treatment

schedule

saline gtven on a divided

on each day) plus mitomycin

in 6%

(4/61)

(24/61),

34% (IOn9). study were45 enrolled

histologtc

mg/m’per

week (90% of the projected but manageable.

1 .0GiYmm3) and thrombocytopenia toxicity

and clinically

each (13%).

and a peripheral

cases (27%). Improved

treated,

significant

Whether

therapeutic

a randomized

(platelets,

Roizin-Towle

simultaneous

at 30 min. influenced

IO0

plasma

Tumor-tissue by the cisplatin

variability

tn non-small-cell

L. Pirro JP, Hall EJ. Centerfor

University

NY 10032. Radial

College

of plali-

lung cancer.

A lung carcinoma bioreductive

(I Suppl)

the cytotoxic

with

terminal

RSU-1164,

to the aziridine

RB-7040,

substitution

of the alkylating

moiety.

cytotoxicity

in air and hypoxia

with

therapy results in an being evaluated

in

therapy.

RSU-1069

in human

under aerobic

10% cell survival,

A comparison

cells exposed

and rodent

similar results.The cytotoxicity concentrations

that methyl was made

factors, defined

cytotoxicity

of

yielded

to be the ratio of drug

condrtions

were found to be 40,25.

of

to drugs for a 4-h

cells (V-79-379A)

and hypoxic

and

with progressive

of the aerobic and hypoxic

(A-549)

or

and are

RR-88176,andRB-88712.

ring reduced cell killing

period. A direct comparison

in vitro

of nitroimidazoles

in air demonstrated

renal in I7

cultured

rings on the side chain

occurred

in 8 patients

York.

effect of a range of bifunctional

aziridine

of the cytotoxicity

New

S50-S55.

drugs. The drugs tested consisted

nitrofurans

Research,

and Surgeons.

cell line of human orogin (A-549)

alkyl addition

<

Radiological

of Physicians

Res 1990;124

(WBC,

cisplatin

in patients

Studies with bifunctional bioreductive drugs. II. Cytotoxicity assayed with A-549 lung carcinoma cells of human origin

Measurements

trial versus standard-dose

between

concentrations

properttes

in tumor-

ng Pt/mg

suggests a great intcrindividual

designated RSU-1069,

was observed

53.89

seem to be poorly

was used to investigate

in this

Dose-limiting

is currently

dose. This finding

in the 62

developed

this type of dose-intensive

platinum

concentrations

regimen

Leukopenia

sensory neuropathy

index in NSCLC

comparative

squamous,

< 25,OOO/mm’)

respectively. ototoxicity

platinum

was observed

ng Pt/mg tn those receiving

was a weak correlation

dose) and 1.5 mp/

of thts combination

pattents was significant

The

and adenocarcinoma, dose intensities

There

Columbia

(20/61).

subtype included

C delivered

The toxicity

m 3% and 8% of patients

day 1 of the overall

for all patients was 29.3 weeks. The

and mitomycm

(75%).

in 33%

large cell. 31% (4/13);

The median survival

mean cisplating

response,

f

at 30

2.5 mg/m’

100 mg/m’ (1.44 f 0.62

difference

25 mg/m’ vs 51.13 f 65.52

mplm2).

concentrations

in patients receivmg

(22.49

of

in

withacompleteresponsebeingachieved

to reviewed

53% of patients (10/19);

tn’per week

for response analysis,

of cases and a partial

response according

of cisplatin

C given at a dose of 8 mg/m’on

concentrattons

num tumor-diffusion

days I and 8 schedule (100 mg/m’

each cycle. In 61 patients evaluable responseratewas39%

consisted

no significant

by means

The procedure did no1

plasma platinum

than in those receiving

whereas

and tumor-tissue

a pharmacokinetically

(200 mg/m’per

Total

(0.49 f 0.23 pg Wml) pg Pt/ml), receivmg

1990;27:243-7. m advanced

concentrations

lower (P .z 0.01)

infusion,

biopsy specimens were

spectrophotometry.

mitt were significantly

tissue plattnum

ISOMuirRoad,

dose intensity

cisplatin

M, Ahn DK et

induce any comphcation.

of the cisplatin

obtained

which

result in

18, and 8. respectively,

for

thefouragentsRSU-1069,RSU-1164,RB-88172,andRB-881761es1ed

Carboplatin and etoposidc in advanced lung cancer: - A phase I study Liippo

K, Nikkanen

Chemother

Pharmacol

This phase

I study

dose of carboplatin to recommend 100

V, Heinoncn

ofthe

of Dlseaws

E. Deporm~nl

of Turku, Paimto /lospiral,

Chest. Universiry

SF-21540

Preilila.

Cancer

the maximal

tolerated

(Car) together with a fixed dose of etoposide (E) and dose [or a phase II study. The dose of E was

mgfm’given i.v. on days l-3, and the starting dose of Car was 200

mgfm’given toxicity

iv. on day

developed

I. The

dose was escalated until WHO

after two treatment

trial. The maximal tological

tolerated

mg/m’Car.

toxicity

toxtcity

of the combination

Myelosuppression

of WHO

grade 4

cycles in more than one-third

was reached at

was moderate,

grade 4 was encountered

and hema-

in one of live

pattents at 475 mg/m* and in two out of five patients at 500 mg/m*. main

loxic

quency

effects

were

leucopema

of treatment-related

caused by treatment. the plalelet

and thrombocytopenia.

inrections

The fre-

clearance.

overall correlation One complete

betwen

response and

three partial responses were achicvcd after two trcatmentcyclcs. on the results of the present study, the dose of carboplatin with

100 mg/m2eposidc

The

was low and no deaths were

There was a significant

nadtr and creatinine

of

enteredthe

the patients. A total of 33 patients wtth advanced lung cancer a dose or500

given on days l-3)

cells. It has been suggested that under aerobic condittons ring

is primarily

responsible

conditions,

the aziridine

under hypoxic duced 2-nitro

Based

(combined

recommended

for phase II

Sculier Jules

JP, Klastcrsky Bordel,

Pupl

J-L, Cupissol

Service

da

Maladies

1’Aiguelongue. macol

D. Gestin-Boyer Respirarorres.

F-34059

Monfpellrer

C, Bres J. Serrou B, Michel Rue du Major Ceder.

Flandre,

F-B.

(The Netherlands) Two

prospectively

of platinum

Phar-

were studied

in two groups of eight patients who were suffering

advanced non-small-cell cnt schedules of cisplatin

lung cancer. Treatments administration

including

with

a rtet al.,

J, Libert

P et al. Servrce de Medecine, I, B-1000

trials were conducted,

I g/n?; doxorubicin

1.4 mg/m2: all i.v. on day I: every

CAVi

plus vindcsine

3 weeks)

with

or without

was used alone. In 45 cvaluable

wereobserved study, CAVi

(13%;

tericin

was potentiated

B entrapped

might

Among

cisplatin.

as salvage

patients.

6 objective 5.1-20.8).

liposomes

I1 evaluable

Confidence

responses

In thesecond given

consisted of amphomade of egg lecithin,

patients,

Limits:

with

In the first study,

in the molar ratio 4:3:l

resistance

controlled

combination

(cyclo-

vincrtstine

after firs1 lint treatmenl

Ampholiposomes

into sonicated

and stearylamine

overcome

Cancer

with 2 mgfkg of ampholiposomes

not increased. These preliminary encourage

45 mp/m*;

ConfidenceLimitsCL.):

iv.. 24 h prior to chemotherapy. cholesterol

In&u!

Lung

testing the CAVi

(adriamycin)

therapy for small cell lung cancer (SCLC) etoposide

Bruelles.

1990;6: 110-18.

consecutive

phosphamide

(lipid

6 objective

23.4-83.3)

concentraresponses

and toxicity

was

results suggest that ampholiposomes

to chemotherapy

in SCLC

and should

studies.

Chemotherapy or not in advanced non-small cell lung cancer? Cellerino

and plasma concentrations

combined

agent (I.J. Stratford

Hopi@1

Cancer Chemother

1990:27:72-5.

Tumor-tissue

the

whereas

1986).

Rue Heger-Bordet

were observed (55%;

Tumor-tissue and plasma concentrations of platinum during chemotherapy of non-small-cell lung cancer patients

moiety

toxicity,

A phase II study evaluating CA Vi (cyclophosphamide, adriamycin, vincristine) potentiated or not by amphotericin B entrapped into sonicated liposomes, as salvage therapy for small cell lung cancer

tion: 20 mg/ml).

studtes is 450 mg/m’.

for aerobic

motety produces a bifunctional

Br. J. Cancer 53,339-344,

1990;27:229-33.

was carried out to determine

the optimal

in A-549 aziridine

from

two differ-

(25 vs IOU mg/m’on

day 1)

Universira

R. Tummarello di Ancona,

D. Piga

Ospedale

Cancer (The Netherlands)

A. Direfrore

di Ibrrelre.

Oncologia

l-60/00

Clinico,

Ancona.

Lung

advanced

non-

1990:6:99-107.

The value of chemotherapy

(CT)

in patients

small cell lung cancerrcmainscontrovcrsial.

In

with

the past 10yearsresulls