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1109
Phase II Clinical Trial of SKI-2053R, a New Platinum
Analog, in the Treatment of Patients with Advanced
Gastric Adenocarcinoma
Noe K. Kim, M.D.
Seock-Ah Im, M.D.
Dong-Wan Kim, M.D.
Moon H. Lee, M.D.
Chul W. Jung, M.D.
Eun K. Cho, M.D.
Jong T. Lee, M.D.
Jin S. Ahn, M.D.
Dae S. Heo, M.D.
Yung-Jue Bang, M.D.
Department of Internal Medicine, Seoul National
University College of Medicine, Seoul, South Korea.
BACKGROUND. SKI-2053R (SK Chemicals, Kyungki-Do, South Korea) is a new platinum derivative with antitumor activity against various cell lines, including cisplatin-resistant tumor cell lines. Preclinical studies have suggested that it is less
nephrotoxic than cisplatin. This study evaluated the efficacy and toxicity of SKI2053R in the treatment of patients with advanced gastric adenocarcinoma.
METHODS. Thirty-seven patients with advanced gastric adenocarcinoma that was
unresectable or metastatic were treated. No prior chemotherapy or radiotherapy
was allowed. Patients received SKI-2053R 360 mg/m2 by 1-hour infusion on Day 1.
After the first cycle, subsequent doses were adjusted according to the toxicity.
Courses were repeated every 28 days.
RESULTS. Thirty-five patients were evaluable for response and toxicity. Six patients
achieved a major response (17%; 95% confidence interval, 8 –33%); 2 were complete and 4 were partial responses. The median duration of response was 7.2
months, with a range of 1–20 months. Patients could tolerate the treatment without
significant toxicity. No patients had Grade 3 or 4 toxicity. The most frequent
toxicity was Grade 1 or 2 proteinuria (26% of cycles), but it was mild and transient.
Leukopenia, thrombocytopenia, azotemia, nausea and vomiting, and neurotoxicity
were not frequent. These low toxicity profiles indicated that the dose of SKI-2053R
could be increased in future studies.
CONCLUSIONS. SKI-2053R was active in the treatment of patients with gastric
adenocarcinoma and had favorable toxicity profiles. Cancer 1999;86:1109 –15.
© 1999 American Cancer Society.
KEYWORDS: SKI-2053R, gastric carcinoma, chemotherapy, clinical trial, Phase II
study.
G
Presented in abstract form at the 33rd annual
meeting of the American Society of Clinical Oncology, Denver, Colorado, May 1997.
Supported by Grant HMP-98-D-1-0002 from the
’98 Good Health R & D Project, Ministry of Health
and Welfare, Republic of Korea.
Address for reprints: Noe Kyeong Kim, M.D., Department of Internal Medicine, Seoul National University College of Medicine, 28, Yongon-dong,
Chongno-gu, Seoul, 110-744, South Korea.
Received December 7, 1998; revision received
April 22, 1999; accepted April 22, 1999.
© 1999 American Cancer Society
astric adenocarcinoma is the most common malignancy in Korea,1 and it is one of the most prevalent malignancies in many
countries.2 The prognosis of gastric adenocarcinoma is very grave;
only 20 –30% of patients survive longer than 5 years. The causes of the
poor prognosis are adjacent organ invasion and distant metastasis at
diagnosis. Thus, the development of effective chemotherapeutic
agents for locally advanced and metastatic gastric carcinoma is essential.
For many years, a few single agents, such as 5-fluorouracil, doxorubicin, mitomycin C, and nitrosourea, have been considered to have
significant antitumor activity in patients with gastric carcinoma.3
However, the response rate has been less than 30% and complete
remission has been rare. To improve treatment outcomes, several
combination chemotherapy regimens with these agents have been
tried. FAM (5-fluorouracil, doxorubicin, and mitomycin C) chemo-
1110
CANCER October 1, 1999 / Volume 86 / Number 7
FIGURE 1. Structures of SKI-2053R, cisplatin, and carboplatin are shown.
therapy showed a response rate of 42% in a nonrandomized Phase II study.4 There was no evidence that
combination chemotherapy could increase the survival rate of patients.5
In mid-1980s, it was suggested that cisplatin was
effective in treating gastric carcinoma, with a response
rate of 19%.6 Recently, some cisplatin-based combination chemotherapy regimens showed high response
rates of 40 –70%.7–11
Despite the effectiveness of cisplatin against gastric carcinoma, there were two major problems with
this agent. First, cancer cells showed primary or acquired resistance to cisplatin.12 Second, significant
side effects were observed, such as severe nausea and
vomiting, nephrotoxicity, and neurotoxicity.13 To
overcome these drawbacks of cisplatin, extensive efforts have been made to develop new cisplatin analogs
with equivalent or greater antitumor activity and
lower toxicity.14 –17 Among them, carboplatin has reduced renal and gastrointestinal toxicities as compared with cisplatin.14,18 However, carboplatin has no
enhanced therapeutic efficacy over cisplatin and has
not circumvented acquired resistance to cisplatin due
to its cross-resistance.19
SK Chemicals (Kyungki-Do, South Korea) has developed many cisplatin analogs, including SKI-2053R
(Fig. 1). Preclinical studies with SKI-2053R showed
antitumor effects on various cancer cell lines comparable to cisplatin.20 –22 Moreover, it was effective
against gastric carcinoma cell lines. SKI-2053R especially showed an antitumor effect on L1210-CPR cells,
which are from an experimentally induced, cisplatinresistant cell line.20,21 No remarkable toxicity was
found in a general pharmacologic evaluation of pre-
clinical trials.23 A toxicity evaluation of beagle dogs
showed a milder nephrotoxicity than cisplatin but
showed major toxicity in bone marrow suppression
and mucositis.24 It was expected that bone marrow
suppression and mucositis would be dose-limiting
toxicities in clinical trials.
We performed a Phase I clinical trial based on
these preclinical data.25 SKI-2053R was administered
intravenously as a 1-hour infusion on Day 1 and every
4 weeks after that. The starting dose of the Phase I
study was 40 mg/m2, which was one-tenth of LD10 in
mouse (LD10 in mouse was 380 mg/m2). The dose of
drug was increased up to 480 mg/m2 using a modified
Fibonacci method. There was no significant toxicity
with dosages up to 360 mg/m2. At 480 mg/m2, twothirds of patients developed Grade 4 hepatotoxicity,
Grade 3 leukopenia, thrombocytopenia, Grade 2
azotemia, and proteinuria. Other toxicity included
nausea/vomiting and mucositis. It was suggested that
peripheral neuropathy could be present with long
term administration. By these results, the initial dose
of Phase II clinical trial was recommended as 360
mg/m2 (75% of maximal tolerable dose, 480 mg/m2).
The purpose of this clinical trial was to evaluate
the efficacy and toxicity of the SKI-2053R chemotherapy in patients with advanced gastric adenocarcinoma.
PATIENTS AND METHODS
This study was performed at the Seoul National University Hospital (SNUH), Seoul, South Korea, and patients were accrued only at SNUH.
Patients were eligible if they had histologic evidence of unresectable or metastatic gastric adenocarcinoma. Patients were required to have measurable
disease, which was defined as follows: 1) a tumor mass
that could be evaluated by physical examination in
two perpendicular dimensions (e.g., skin nodule or
lymph node), 2) a clearly measurable lung nodule on
chest radiography, or 3) a hepatic lesion with a maximal dimension of over 2 cm that could be measured
by computed tomography (CT) scan. Prior surgical
treatment, such as gastrectomy, was allowed, but only
if it was performed at least 3 weeks before enrollment
in the study. Patients’ ages ranged from 20 to 70 years.
All patients signed an informed consent form. Patients
were required to have Eastern Cooperative Oncology
Group (ECOG) performance status of 0 –2 and a life
expectancy of 3 months or longer. Adequate hematologic function (hemoglobin level $6.2 mmol/liter [10
g/dL]), white blood cell count $4.0 3 109/liter, platelet
count $100 3 109/liter), renal function (serum creatinine level #132.6 mmol/liter [1.5 mg/dL] or creatinine
clearance $65 mL/min), and hepatic function (biliru-
SKI-2053R for Gastric Adenocarcinoma/Kim et al.
TABLE 1
Dose Modification of Subsequent Cycle According to the Toxicity
after the First Cycle
Leukocyte
(3 109/liter)
Platelet
(3 109/liter)
Hepatotoxicity
Dose
.3.0
2.0–3.0
,2.0
.75
50–75
,50
Grade 0–1
Grade 2
Grade 3
400 mg/m2 (escalation by 11%)
360 mg/m2 (same as first cycle)
320 mg/m2 (reduction by 11%)
bin level #25.65 mmol/liter [1.5 mg/dL] or serum alanine aminotransferase/aspartate aminotransferase
[ALT/AST] level less than 2 times of reference value)
were required.
No prior chemotherapy, immunotherapy, or radiation therapy were allowed. Patients with the following conditions were excluded: 1) active bacterial infection that required antibiotic treatment; 2) the
presence of psychiatric disease, brain metastasis, or
seizure disorder; or 3) pregnancy or lactation.
Treatment was administered in the inpatient setting. SK Chemicals provided SKI-2053R. SKI-2053R
was administered by intravenous injection into a peripheral vein over 1 hour on Day 1. It was diluted with
500 mL of 5% dextrose water. The 1500 mL of 0.9%
saline was infused over 12 hours before the administration of SKI-2053R. To prevent emesis, 8 mg of ondansetron were given by intravenous route 3 times (15
minutes before, 4 hours after, and 8 hours after SKI2053R infusion). The course was repeated every 28
days. The starting dose was 360 mg/m2 and subsequent dosage was modified according to the hematologic and hepatic toxicity after the first cycle, as shown
in Table 1.
Pretreatment evaluation included taking a complete history, physical examination, and documentation of performance status. Pretreatment laboratory
evaluation included a complete blood count; partial
thromboplastin time; prothrombin time; urinalysis
(specific gravity, pH, albumin, glucose, ketone, blood,
urobilinogen, bilirubin, nitrite, and microscopy);
blood chemistry, including liver function tests (calcium, phosphate, magnesium, glucose, uric acid, blood
urea nitrogen, creatinine, cholesterol, protein, albumin, bilirubin, alkaline phosphatase, ALT/AST, sodium, potassium, and chloride); and a viral hepatitis
marker study (hepatitis B surface antigen, antibodies
to the hepatitis B surface antigen, antibodies to the
hepatitis B core antigen, and antibodies to the hepatitis C virus). All patients were evaluated with 12-lead
electrocardiogram (EKG), audiogram, and stool occult
blood test. Measurement of creatinine clearance by
24-hour urine collection was performed if it was indi-
1111
cated. Chest radiograph was performed on every patient. CT scan and other studies were performed to
measure lesions before treatment. During the first 4
weeks of the study, history-taking, physical examination, and complete blood count and blood chemistry
were performed every week. These studies were performed every 4 weeks while patients were on therapy.
Partial thromboplastin time and prothrombin time
were evaluated every 2 weeks. Urinalysis, 12-lead EKG,
and creatinine clearance test were performed every 4
weeks. Chest radiograph, stool occult blood test, CT
scan, and other studies to measure the lesion were
performed at the fourth week of study and then every
4 – 8 weeks. Audiogram was obtained at the end of
treatment.
The evaluation of tumor response was performed
every 4 weeks. The criteria for response were as follows: 1) A complete response (CR) was defined as
disappearance of all the evidence of tumor for at least
4 weeks and no evidence of newly developed lesions.
2) A partial response (PR) was defined as a greater
than 50% reduction in the sum of the products of the
longest perpendicular dimensions of indicator lesions
for a period of at least 4 weeks, and no evidence of
enlargement of other lesions or development of new
lesions. 3) Stable disease (SD) was defined as a less
than 50% reduction or less than 25% increase in measurable tumor area and no evidence of newly developed lesions for at least 4 weeks. 4) Progressive disease
(PD) was defined as a greater than 50% increase in the
sum of the products of the longest perpendicular dimensions of indicator lesions or the presence of newly
developed lesions. The evaluation of treatment efficacy was performed at the end of treatment. The efficacy of treatment was defined as the best response of
tumor during treatment.
Toxicity was graded according to the World
Health Organization scoring system of Miller et al.26
Periodic history-taking, physical examination, and
laboratory tests were performed to evaluate toxicity.
Toxicity was properly managed if it occurred.
Treatment was stopped if the disease progressed,
Grade 4 toxicity occurred, the ECOG performance status of patients was 4, or the patient refused further
treatment.
Statistical Analysis
The trial was designed by using a two-stage procedure.27 Assuming a true response rate of at least 20%,
initially 14 patients were accrued. If no response was
observed, the trial would be closed because if the true
response rate was at least 20%, then the probability of
obtaining no response in 14 patients was less than
0.05. The decision was made to continue the study if at
1112
CANCER October 1, 1999 / Volume 86 / Number 7
TABLE 2
Patient Characteristics
Characteristic
No. of patients
Total no. of patients
Evaluable for response
Evaluable for toxicity
Ineligible
Age, yrs
Median
Range
ECOG Performance status
0
1
2
Men/women
Prior therapy
None
Surgery
Site of measurable lesion
Intraabdominal lymph nodes
Cervical lymph nodes
Liver mass
Ovarian mass
Intraabdominal mass
Pelvic mass
37
35
35
2
53
33–65
5
27
5
28/9
26
11
27
6
14
2
1
1
ECOG: Eastern Cooperative Oncology Group.
least 1 treatment response was observed and 11 additional patients were to be included according to the
rules, to obtain an accuracy of 0.10 of the final response rate; however, accrual was continued to a total
of 35 patients so that the response proportion would
be better defined. According to this design, the probability of completing the trial was greater than 95% if
the true response rate was at least 20%. The proportion of patients who responded was used to estimate
the true response rate, with a 95% confidence interval
based on a multistage testing procedure. Survival
times were calculated from the start of chemotherapy
until death. Duration of response was evaluated depending on response: PR duration was calculated
from the start of chemotherapy to the date of PD; CR
duration was calculated from the date of the evaluation of the CR to the date of PD. Actuarial survival was
determined by the Kaplan–Meier method.28
RESULTS
Baseline Characteristics of Patients
Patients’ characteristics are listed in Table 2. Thirtyseven patients were accrued from January 1995 until
August 1996 at SNUH. Thirty-five patients were evaluable for response and toxicity. Two patients were ineligible due to inadequate hemoglobin level and hepatic transaminase (ALT/AST) level. The median age
of patients was 53 years (range, 33– 65 years). Twentyeight patients were male and 9 were female. Most of
the patients had good performance status. No patient
had received prior chemotherapy or radiotherapy.
Eleven patients had received palliative surgical treatment before SKI-2053R treatment. All patients had
bidimensionally measurable lesions. The measurable
lesions of patients were intraabdominal lymph nodes
(27 patients), cervical lymph nodes (6 patients), metastatic lesions in liver (14 patients), ovarian masses (2
patients), an intra-abdominal mass (1 patient), and a
pelvic mass (1 patient).
Response
The median number of cycles of chemotherapy was 2
(range, 1–17cycles). Nine patients completed three or
more courses of chemotherapy.
Thirty-five patients were evaluable for response.
Six of 35 evaluable patients achieved major responses
(17%; 95% confidence interval, 8 –33), including 4 partial (11%) and 2 complete responses (6%). Partial responses were seen after a median of 2 cycles (range,
1–2 cycles) and complete responses were seen after 6
and 8 cycles. The duration of response ranged from 1
to 20 months (median, 7.2 months), with partial responses that lasted for 1–20 months (median, 7.2
months) and complete responses that lasted for 3.2
and 6.2 months. Responses were seen in patients with
liver mass, intraabdominal lymph nodes, and cervical
lymph nodes.
Complete responses were observed in two patients with unresectable perigastric lymph nodes. One
patient achieved a complete response after 8 cycles of
therapy. The patient subsequently underwent gastrectomy to control the primary lesion. There was no
evidence of residual tumor on surgical pathology.
However, the disease recurred in cervical lymph nodes
and liver 3 months after operation. The other patient
achieved a complete response after six cycles of therapy. When the operation was recommended to control
the primary lesion, the patient refused. The disease
recurred in the stomach 6 months after the complete
response.
Four patients achieved partial responses. Three of
these patients had metastatic liver disease and one
patient had cervical and perigastric lymph node disease. SKI-2053R was administered until disease progressed. Three have died of disease and one remains
alive with disease.
The median duration of survival from the first
cycle of chemotherapy was 9.1 months (range, 1.4 –
34.21 months) for all patients and 20.6 months (range,
9.1–34.21 months) for responders (median follow-up
time, 22.2 months). Eleven patients survived for more
SKI-2053R for Gastric Adenocarcinoma/Kim et al.
1113
TABLE 4
Nonhematologic Toxicity per Patient (Total of 35 Patients)
Grade 1
FIGURE 2. Kaplan–Meier overall survival is shown for all eligible patients (35
patients, 10 censored). The median survival was 9.1 months. Marks indicate
last follow-up.
Grade 2
Grade 3
Grade 4
Toxicity
No.
%
No.
%
No.
%
No.
%
Nausea/vomiting
Diarrhea
Constipation
Stomatitis
Hepatic
Elevation of BUN/Cr
Proteinuria
Hematuria
Peripheral neuropathy
Auditory neuropathy
Alopecia
19
4
5
1
5
4
10
10
5
0
1
54
11
14
3
14
11
29
29
14
0
3
8
0
0
0
2
0
18
0
0
0
0
23
0
0
0
6
0
51
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
BUN: blood urea nitrogen; Cr: creatinine.
TABLE 5
Renal Toxicity per Cycle (Total of 94 Cycles)
TABLE 3
Hematologic Toxicity per Cycle (Total of 94 Cycles)
Grade 1
Grade 2
Grade 3
Grade 1
Grade 4
Toxicity
No.
%
No.
%
No.
%
No.
%
Anemia
Leukopenia
Thrombocytopenia
30
13
3
32
14
3
12
3
0
13
3
0
0
0
0
0
0
0
0
0
0
0
0
0
Grade 2
Grade 3
Grade 4
Toxicity
No.
%
No.
%
No.
%
No.
%
Elevation of BUN/Cr
Proteinuria
Hematuria
4
19
12
4
20
13
0
24
0
0
26
0
0
0
0
0
0
0
0
0
0
0
0
0
BUN: blood urea nitrogen; Cr: creatinine.
than 12 months and 7 patients survived for more than
24 months. Actuarial survival is shown in Figure 2.
Toxicity
Thirty-five patients were assessable for toxicity and a
total of 94 cycles were delivered. Hematologic and
nonhematologic toxicities are listed in Tables 3 and 4.
Patients tolerated the treatment without serious toxicity. Grade 3– 4 toxicity was not experienced by any
patient, and none of the patients were removed from
the study due to toxicity. Dose reduction was not
required in any of the cycles, and the dose was escalated for 12 patients (34%).
The most common hematologic toxicity was anemia. Grade 1 and 2 anemia occurred at 32% and 13%
of treatment cycles, respectively. Leukopenia of Grade
1 or 2 was experienced in 17% of cycles. Thrombocytopenia was experienced in 3% of all cycles.
The most common nonhematologic toxicity was
proteinuria of Grade 1 or 2. Proteinuria occurred in 28
of 35 patients (80%), including 10 patients with Grade
1 proteinuria and 18 patients with Grade 2 proteinuria
(defined as 11 ; 111 on urine stick test; 0.3–1.0
g/dL). Despite the frequency of proteinuria, Grade 2
proteinuria occurred in only 24 of 94 cycles (26%)
(Table 5). No patient experienced symptomatic proteinuria. When the urinalysis was performed serially,
the proteinuria resolved completely after the treatment. Another renal toxicity was Grade 1 hematuria
(29%), which was transient. Azotemia occurred in 4 of
35 patients (11%) and was Grade 1 in all cases.
Gastrointestinal toxicity included nausea/vomiting, diarrhea, constipation, and stomatitis of Grade 1
or 2. Mild nausea/vomiting was observed transiently
in 27 of the 35 patients and could be well controlled
with antiemetic medication. No patient experienced
Grade 3 or 4 nausea/vomiting. Diarrhea, constipation,
and stomatitis were reported infrequently and were
mild.
Reversible elevation of hepatic transaminase of
Grade 1 or 2 occurred in 7 patients (20%). Transient
alopecia was reported in one patient.
Neurotoxicity was rare and transient. Five patients
had Grade 1 peripheral neuropathy but tolerated it
well. All of them experienced peripheral neuropathy
during the first cycle of treatment, and it completely
resolved subsequently. Nine patients received more
1114
CANCER October 1, 1999 / Volume 86 / Number 7
than three cycles of treatment and did not experience
neuropathy. Ototoxicity did not occur in any patient.
All chemotherapy toxicities were reversible, and
there were no chemotherapy-related deaths.
DISCUSSION
Cisplatin is an effective chemotherapeutic agent in the
treatment of advanced gastric adenocarcinoma. However, its clinical usefulness has frequently been limited
by undesirable side effects13 and by the development
of resistance.12 Carboplatin has modified the problems of toxicity, but it does not possess the ability to
overcome cross-resistance.19 Therefore, there is a
pressing need to identify new active agents that can
overcome toxicity and resistance in the treatment of
gastric carcinoma patients.
SKI-2053R demonstrated antitumor activity superior to that of cisplatin against a variety of tumor
cell lines, including cisplatin-resistant tumor cell
lines.20 –22 Preclinical studies suggested that it was less
nephrotoxic than cisplatin, and bone marrow suppression was a predominant toxicity in animals.24 A
Phase I clinical trial showed that the dose-limiting
toxicities of this agent were hepatotoxicity and bone
marrow suppression.25 Based on these results, we expected that SKI-2053R had antitumor activity in gastric carcinoma with less nephrotoxicity than cisplatin.
We performed this study to evaluate the efficacy and
toxicity of SKI-2053R in patients with advanced gastric
adenocarcinoma.
The result of this study showed that SKI-2053R
had antitumor activity comparable to that of cisplatin
in gastric adenocarcinoma. Objective responses occurred in 6 of 35 evaluable patients (response rate,
17%). The response rate in this study was similar to
that of single-agent treatment with cisplatin.6 Two
patients achieved complete responses, and one of
them had no evidence of disease on surgical pathology. Responses occurred in metastatic sites as well as
regional lymph nodes. Although the median duration
of response was 7.2 months, the response was more
durable in some patients.
SKI-2053R could be safely administered to all patients. The toxicity profiles of this agent were more
favorable than those of other platinum agents. No
patient experienced Grade 3 or 4 toxicity. Dose reduction due to toxicity was not required in any of the
cycles.
Bone marrow suppression, which is common with
carboplatin,29 was generally mild. Anemia of Grade 1
or 2 was relatively common. Thrombocytopenia occurred in only 3% of cycles.
Nephrotoxicity was generally milder with SKI2053R than with cisplatin, as expected in preclinical
and Phase I studies. In spite of less aggressive hydration, the azotemia was less frequent and milder than
with cisplatin, and cumulative nephrotoxicity did not
appear. Only Grade 1 azotemia occurred in 11% of the
patients. However, mild proteinuria was frequent, and
it was the most remarkable toxicity in this study. Proteinuria occurred in 26% of cycles. However, the grade
of proteinuria was mild, and the toxicity was transient.
Grade 3– 4 proteinuria did not occur in any patient.
When we performed serial urinalysis of patients with
proteinuria, the results showed that most proteinuria
occurred during the first week of the cycle and gradually decreased with time. Proteinuria completely resolved after discontinuation of treatment for all patients. We concluded that proteinuria was mild and
reversible, but further evaluation is warranted.
Nausea/vomiting was infrequent and mild with
SKI-2053R. It may reflect the antiemetic effect of ondansetron. Other gastrointestinal toxicities, including
diarrhea, constipation, and stomatitis, were also uncommon with this agent.
Neuropathy was not significant. Ototoxicity, a cumulative and irreversible side effect of cisplatin,13 was
not observed with SKI-2053R. Peripheral neuropathy
was also a cumulative side effect of cisplatin. However,
only 5 patients had Grade 1 peripheral neuropathy,
and they tolerated it well. It was remarkable that neuropathy occurred only in the first cycle and that it was
reversible in all cases. Cumulative neurotoxicity was
not reported even in the patients who had more than
three cycles of treatment.
Low toxicity profiles suggested that the starting
dose of this agent could be increased up to 400 mg/m2
in further trials. Despite low toxicity, the response rate
was comparable to that achieved with cisplatin. It was
expected that SKI-2053R might show antitumor activity superior to that of cisplatin at higher doses. Preclinical studies showed that continuous infusion (over
12–24 hours) of this agent was more effective than
infusion for a short period (over 1–3 hours).30 Phase I
and II clinical trials with continuous infusion of higher
dose SKI-2053R are being conducted.
In conclusion, SKI-2053R was a safe and active
agent in the treatment of advanced gastric adenocarcinoma patients in this study.
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