C h i n e s e Journa l o l Cancer R e s e a r c h 2(4): 56-59, 1990.

VARIOUS DOSES OF ClSPLATIN (DDP) COMBINED WITH MULTI-DRUG CHEMOTHERAPY FOR ADVANCED MALIGNANT SOLID TUMOR

Wang Qilu : E ~ Feng Fengyi ~ - ~ { ~ Wang linwan : E : ~ f Sun Yan ~x~-~ Zhou lichang J ~ / ~ Wang Cai :=E)~ Xiong Hui , ~ Li Oing ~ Wu Guangqing ~ Su Mei ,-~4~

Cancer Hospital, Chinese Academy ol Medical Sciences, Beijing

Two hundred and thirty-six patinets with various

advanced malignant solid tumors treated by com-

bined chemotherapy with routine doses of eisplatin

(DDP) from 1980 to 1986 are presented. According

to different doses of cisplatin everyday, the patients

were divided into 4 groups: (1) 20 nag/day x 4 - 5,

80 cases; (2) 30 rag/day x 5 1 5, 91 eases; (5) 40 rag/

day $----4, $7 eases; (4) 50 m g / d a y x 2 --- 5, 28 cases.

Each group was repeated for 3 weeks. The effect

and toxicity were analysed and compared with 22

cases treated by single D D P in 1975. The response

(CR+PR) rate was 39.2% in 194 evaluated patients.

The response rate was similar in group 20 nag an:l

single D D P (29.2% and 27.3%). The response rate

was Iowex than that of group 30 rag, 40 mg, and

50 mg 45.4% and 50,~) (P<0.05) . The remissions

in various groups were not significantly different.

The toxicity of combined chemotherapy was not

severe. 91.1% of patients had nausea and vomiting.

There was no statistical difference in the various

groups. Bone marrow suppresion was less in single

D D P group than that of combined chemotherapy

group (P<0.05), D D P 30---50 mg l / d x S I 3 was

better than H D - D D P in some patients.

From 1980 to 1986, 236 various advanced

malignant solid tumors were treated with com-

bined chemotherapy including various routine

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doses of Cisplatin (DDP). The therapeutic

effects and toxicity were reported as follows.

MATERIALS A N D M E T H O D S

All cases received over 160 mg with obser-

vation time over 14 days in this study.

The patients included 163 men and 73 women from 16 to 78 years old, those of 31--60

years old occupying 76.4%.

The total number of cases was 236, among

whom 56 were operated, 117 received radio-

therapy and/or chemotherapy and 63 were

untreated.

The total dosage of DDP was administered

from 160 mg to 620 mg, 2 0 0 - - 3 0 0 mg occupy-

ing 60.2%.

According to different daily doses of DDP,

these patients were divided into 4 groups; (1)

20 mg/day X 4 - - 5 in 80 cases; (2) 30 rag/day X

3 - - 5 in 91 cases; (3) 40 mg/day × 3 - - 4 in 37

cases; (4) 50 mg/day × 2 1 3 in 28 cases. The

above mentioned dosage was repeated every 3

weeks. Two cycles were the most (72.5%).

Among 236 cases, 196 cases were treated with

three drugs of combination chemotherapy.

The drugs of combined chemotherapy in this study were:

PMF (DDP, MMC, 5FU or FT207) for adenocarcinoma of the lung, renal, gastric or colorectal cancer and metastatic carcinoma. PC (DDP, CTX) etc. for squamous carcinoma of the lung and sarcoma of soft tissue; PMF (DDP, MTX, 5FU or FT207) for large cell undifferen- tial carcinoma of the lung and breast carcinoma PA (DDP, ADM) etc. for SCLC; FCV (DDP, CTX, VCR) for melanoma; PPV (DDP, PYM, VCR) for carcinoma of testis, malignant lymp- homa; PP (DDP, PYM) etc. for esophageal car- cinoma, NPC; PA_+V (DDP, ADM,+VCR) for osteogenic sarcoma.

The laboratory examination in these pa- tients included the routine of blood, the urina- lysis, the liver function, BUN, Creatining, EKG,

chest film, renalgraphy etc.. When these pa- tients were treated with I)D,P, 1000---1500 ml of 5% glucose solution and 5% glucose N.S solu- tion were needed for hydration; some medicine should be given to decrease the vomiting if

necessary.

RESULTS

Evaluation of the response: According to the international standard, including complete remission (CR), partial remission (PR), stable (S) and progressive (P); the period of remission was from begining treatment to recurrence or metas- tasis. 194 cases were evaluated in this study. The objective response rates to various doses of DDP with multi-drug chemotherapy regimens for malignant solid tumors were shown in Table

1.

Table 1. The objective response rates and period o] remission of combination DDP and other durgs chemotherapy Jor malignant solid tumors

T y p e o f n e o p l a s m No. of No. of

evaluated cases

cases

R e s p o n s e ( c a s e s ) C R Q - P R R e m i s s (%) (month)

C R P R S P

A d e n o c a r c i n o m a o f l u n g 52 48 . . . . 17 24 7 35.4 1 - 1 0

S C C of l u n g 22 18 . . . 7 9 2 38.9 2-4

L a r g e ce l l u n d i f f e r e n t i a l I f 10 . . . 1 5 4 10 2 c a r c i n o m a of l u n g

S C L C 9 9 . . . 2 4 3 22.2 2-8

B r e a s t c a n c e r 36 26 3 9 9 5 46.2 1-11

M e l a n o m a 17 8 1 4 2 1 62.5 1-11

C a r c i n o m a o f t e s t i s 12 5 . . . 5 . . . . . . 100.0 5 -60

S a r c o m a o f s o f t t i s s u e 9 8 . . . 2 3 3 25.0 4 -8

R e n a l c a n c e r 8 8 . . . 1 6 1 12.5 6

E s o p h a g e a l c a n c e r 7 7 1 2 3 1 42.9 4-13

M e t a s t a t i c c a n c e r 8 8 1 3 3 1 50.0 2 -8

N P C 10 9 1 5 1 2 66.7 3-12

C o l o r e c t a l c a n c e r 9 6 1 1 2 2 33.3 8 -9

Gastr i c c a n c e r 5 4 . . . . . . 1 3 . . . . . .

O s t e o s a r c o m a 4 3 . . . 3 . . . . . : 100.0 1 .5-4

L y m p h o m a 5 5 . . . 3 2 . . . 60.0 6-14

O t h e r 13 12 . . . 3 8 1 25.0 5-12

T o t a l 236 194 8 66 62 36 39.2

SCLC: small cell lung cancer; SCC: squamous cell carcinoma; NPC: nasopharyngeal carcinoma.

57

The CR+PR rate of undlfferential carci-

noma of the lung were evidently lower than that

of squamous or adenoid carcinoma of the lung

with P<0.05.

I f 26 cases of breast cancer, 19 cases had

received RT and/or CT before, the objective

response rates were 46.2%. 5 cases of malignant

lymphoma, who had failed to respond to regular

treatment before, PR were obtained in 3 cases.

Partial repair was achieved in 2 eases with me-

tastasis of bones. The results showed that DDP

may be an effective drug of second line.

The period of remission in 76 effective cases

was 1 to 60 months, not related to the different

dosage of DDP.

Toxicity

The toxic reactions noted in these DDP

combination regimens are listed in Table 2 with

the following characteristics.

Nausea and vomiting were encountered in

91.1% of cases, discontinuation of treatment in

a few cases, the relationship between the dosage

of DDP and nausea and vomiting (P>0.05) were

not obtained.

Hematologic toxicity accounts for 57.2% in

all of cases, not severe too. Among them, Leu-

copenia 40.7%, lowest value 1.2 X 109/L thromo

bocytopenia 40.3%, the lowest value 21 × 109/I,.

No statistical significance was obtained in com-

bination groups (P>0.05), but in the bone

marrow suppression, the combination groups

were more severe than that of single DDP group,

Liver function was impaired in 24 eases,

among of them, 1 6 8 4 - 3334 n mol.s-I/L 8 cases,

3551- -6668 n mol.s-I/L 10 cases, over 6685 n

mol.s-t/L 6 cases; after treatment, two patients

in BUN examination was increased at 8.7

mmol/L, 8.9 mmol/L respectively.

Others: Alopecia 5 eases, diarrhoea 2 cases,

abdominal distension 1 case, dizziness 2 cases,

oral ulceration 1 case, finger numbness 2 cases.

Table 2. The relationship between the different dosage of DDP and the side efleets

No. o f N a u s e a a n d v o m i t i n g B o n e m a r r o w G r o u p

c a s e s N o n e Mild M o d e r a t e S e v e r e N o r m a l S u p p r e s s

Single DDP 22 3(13.6) 11(50) 5(22.8) 3(13.6) 15(68.2) 7(31.8)

20 m g 8o 8(9.9) 29(30.3) 36(45) 7(8.8) 40(50) 40(50)

30 mg 91 7(7.6) 33(36.3) 35(38.5) 16(17.6) 33(36.3) 58(63.7)

40 m g 37 3(8.1) 13(35.1) 10(27.1) 11(29.7) 18(48.6) 19(51.4)

50 rng 20 3(10.8) 13(46.4) 10(35.7) 2(7.1) 10(35.7) 18(64.3)

DISCUSSION

Literature always showed that the high dose

of DDP, the severe toxicity.X-s As shown in

Table 3, the effect in 30 mg/day, 40 mg/day,

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50 mg/day groups were higher than that of

20 mg/day and single DDP group (P<0.05), but

the toxicity were not severe, therefore, clinical

dosage of DDP with 30 mg /day , 40 rag/day or

50 mg/day were rational.

Table 3.

T y p e of n e o p l a s m

The relationship between dosage o] DDP and clinical ef]eet

No. o f e f f e c t c a s e s / N o , o f e v a l u a t e d e a s e s

20 m g / d 30 m g / d 40 m g td 50 mg/d S i n g l e D D P

A d e n o c a r c i n o m a o f l u n g

SCC o f l u n g

L a r g e ce i l u n d i f f e r e n t i a l c a r c i n o m a o f l u n g

SCLC

Breast cancer

Melanoma

Carcinoma of testis

Sarcoma of soft tissue

Renal cancer

~-sophageal cancer

Metastatic cancer

NPC

Colorectal cancer

Gastric cancer

Osteosarcoma

Lymphoma

O t h e r s

T o t a l

4/12 10/23 3/8 0/5

1/6 3/6 2/5 1/1

0/3 1/6 0/1 1/1

O/1 1/5 1/3

1/]o 5/e 2/3 4/5 o/t

3/4 1/1 1/3

2/2 3/3 1/1

1/4 1/2 0/2

0/4 )/2 0/1 0/4

1/2 1/3 1/2 0/2

214 2/4 113

1/3 3/3 1/2 1/1 2/2

1/3 0/2 1/I 0/1

o/1 0/2 O/l

1/1 I/1 1/1

041 1/1 2/3

1/4 0/4 1/a 1/3 1/7

19/65 33/76 14/33 10/20. 6/22 ~9.2%) (43.4%) (42.4%) (50%) (27.3%)

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