1. Chemotherapy of Colorectal Cancer
Prof. Richard Herrmann
Basel University, Switzerland

2. Chemotherapy of Colorectal Cancer Subjects to be Discussed
potential uses and goals of chemotherapy
the role 5-FU and its modulators
new drugs in colorectal cancer
Xeloda in advanced colorectal cancer, results of phase III
Xeloda in combination with other new drugs, phase I-II
potential for Xeloda in other GI tumors

3. Colorectal Cancer when to use chemotherapy?
preoperatively in rectal cancer (with RT) neoadjuvant situation
postoperatively in stage Dukes C adjuvant situation
in metastatic disease palliative situation
in unresectable liver metastases curative aim (with surgery)

4. Role of 5-FU +/- Modulators in Colorectal Cancer
most active drug for decades
objective response rates of 5-15%
probably superior to no treatment in terms of survival
modulation with folinic acid or methotrexate improves response rate
continuous infusion superior to bolus injection

5. Goals of Chemotherapy in Advanced Colorectal Cancerto
improve symptoms
delay progression
prolong survival
achieve cures?

6. NEW DRUGS IN COLORECTAL CANCER
irinotecan /CPT-11(Campto®)
oxaliplatin (Eloxatin®)
fluoropyrimidines
capecitabine (Xeloda®)
UFT +LCV (Orzel®)

7. Advantages of Oral Chemotherapy
continuous application without the need to install a permanent venous access (port-a-cath)
no operation
no clotting
no infection
no external pump
less doctor visits
higher patient acceptance
lower cost

8. IRINOTECAN other indications: NSCLC, SCLC,
toxicities: bone marrow, diarrhea, alopecia
single agent dose: 350 mg/m2 iv q3w or 125 mg/m2 iv qw x4 every 6 weeks
mechanism of action: inhibition of topoisomerase-I

10. Oxaliplatin 0ther indications: ovarian cancer, NSCLC, other GI?
toxicities: neurotoxicity, bone marrow, GI
single agent dose: 130 mg/m2 q3w or 85 mg/m2 q2w
mechanism of action: DNA inhibition by adduct formation

11. Progression-Free Survival
Median follow-up : 27.7 months
LV5FU2 Oxaliplatin LV5FU2
n = 210 n = 210
median 6.2 months 9 months
% of patients
100 90 80 70 60 50 40
p =
Oxaliplatin + LV5FU2 30 20
LV5FU2 10
months 5 10 15 20 25

12. Rationale for the development of Xeloda®
Oral administration
provides convenient patient-orientated therapy
is capable of mimicking the mechanism of action of continuous infusion 5-FU
lacks complications associated with i.v. administration
Generate 5-FU at the tumour site to maximise antitumour activity and/or improve tolerability
1. Rationale for the development of Xeloda®
Xeloda® (capecitabine), the first of a new class of oral fluoropyrimidines, was rationally designed to mimic continuous infusion 5-fluorouracil (5-FU) and to generate 5-FU preferentially in tumour tissue. The tumour-selective activation of Xeloda® is achieved through exploitation of the high concentrations of thymidine phosphorylase (TP) present in tumour tissue compared with normal tissue.1 The oral administration of Xeloda® enables chronic daily dosing, thus mimicking continuous infusion 5-FU without the complications and inconvenience associated with central venous access. In addition, Xeloda® offers the potential for a convenient, oral, outpatient treatment, which most patients prefer to i.v. therapies.2,3
1. Miwa M, Ura M, Nishida M et al. Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer 1998;34:1274–81.
2. Liu G, Franssen E, Fitch M, Warner E. Patient preferences for oral versus intravenous palliative chemotherapy. J Clin Oncol 1997;15:110–5.
3. Borner M, Schoffski P, de Wit R et al. A randomized crossover trial comparing oral UFT (uracil/tegafur) + leucovorin (LV) and intravenous fluorouracil (FU) + LV for patient preference and pharmacokinetics in advanced colorectal cancer. Proc Am Soc Clin Oncol 2000;19:191a (Abstract 741). o

13. TP activity in human tissues
Colorectal
Gastric
Breast
Cervix
Uterus
Ovarian
Renal
Bladder
Thyroid
Liver
Liver (metastasis)
115 *
291
351 *
309 * 8 13 * 17 18 * 14 23
4. TP activity in human tissues
In a study by Miwa and colleagues, the activity of the three enzymes (cytidine deaminase, carboxylesterase and TP) involved in the conversion of Xeloda® to 5-FU was measured.1 Samples of healthy and tumour tissue were taken from each patient. TP activity was found to be significantly higher in tumour tissue than in healthy tissue from the same individual in breast, gastric, colorectal, cervical, uterine, renal, bladder, thyroid and ovarian cancers. The study also showed that carboxylesterase was found predominantly in the liver and showed little variation in activity between normal and tumour tissue. Analysis of cytidine deaminase revealed that this enzyme was more active in tumour tissue and the liver than in normal tissue adjacent to malignant cells.
1. Miwa M, Ura M, Nishida M et al. Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer 1998;34:1274–81. * 24 37 * 13 11 * 36 35 * 25 27
Healthy tissue
Tumour tissue 16 20 *
TP activity (µg 5-FU/mg protein/hour)
*p<0.05
Miwa M et al. Eur J Cancer 1998;34:1274–81

14. Mean ratios of 5-FU concentrations following administration of Xeloda® or 5-FU in humans22 20 18 16 14 12 10 8 6 4 2
Primary tumor:healthy colon/rectum
Healthy colon/rectum:plasma
Primary tumor:plasma
Mean ratio of 5-FU
6. Mean ratios of 5-FU concentrations following administration of Xeloda® or
5-FU in humans
The tumour selectivity and preferential conversion of Xeloda® in tumour tissue have been confirmed in a ‘proof of principle’ pharmacodynamic study.1 The study included 19 colorectal cancer (CRC) patients who received Xeloda® 1,250mg/m2 twice daily for 5–7 days before tumour resection. The tumour selectivity of Xeloda® was compared retrospectively with that of i.v. 5-FU (500mg/m2 bolus or 1,000mg/m2 24-hour infusion).2 Following administration of Xeloda®, the mean concentration of 5-FU was more than three times higher in primary tumour tissue than in adjacent healthy tissue (p=0.0002). Similarly, the 5-FU concentration was more than 21 times higher in tumour tissue than in plasma. These results confirm the tumour-selective activation of Xeloda®. In contrast, following 5-FU administration the ratios of tumour:healthy tissue, healthy tissue:plasma and tumour:plasma were all close to one, indicating no tumour selectivity.
1. Schüller J, Cassidy J, Dumont E et al. Preferential activation of capecitabine in tumor following oral administration in colorectal cancer patients. Cancer Chemother Pharmacol 2000;45:291–7.
2. Kovach JS, Beart RW Jr. Cellular pharmacology of fluorinated pyrimidines in vivo in man. Invest New Drugs 1989;7:13–25.
Xeloda®1 5-FU2
1Schüller J et al. Cancer Chemother Pharmacol 2000;45:291–7 2Kovach JS, Beart RW Jr. Invest New Drugs 1989;7:13–25

15. Clinical development programme in CRC
Phase I: Europe (two trials)
Phase I: USA
Phase III: Americas
(SO14695)
Phase III: EU, Australasia,
Taiwan (SO14796)
Randomised
phase II
(SO14797)
30. Clinical development programme in CRC
The management of patients with metastatic CRC involves treatment with fluoropyrimidines. The principal representative, 5-FU, is a component of essentially all chemotherapy treatment regimens for metastatic disease. However, there is a significant need for alternatives to i.v. 5-FU offering improved efficacy, tolerability and convenience for patients.
A series of phase I trials determined the MTD of Xeloda®1,2,3 and a phase II dose-selection study in CRC patients identified an intermittent regimen of Xeloda® 1,250mg/m2 twice daily for 2 weeks followed by a 1-week rest period for further clinical development.4
Following selection of the intermittent monotherapy regimen, two large, identical, randomised, phase III clinical trials were conducted to compare intermittent Xeloda® with bolus 5-FU/leucovorin (Mayo Clinic regimen).5,6 Recruitment for a phase III trial evaluating Xeloda® monotherapy as adjuvant treatment for Dukes’ C colon cancer is on target for completion by early 2001.
1. Mackean M, Planting A, Twelves C et al. Phase I and pharmacologic study of intermittent twice-daily oral therapy with capecitabine in patients with advanced and/or metastatic cancer. J Clin Oncol 1998;16:2977–85.
2. Budman DR, Meropol NJ, Reigner B et al. Preliminary studies of a novel oral fluoropyrimidine carbamate: capecitabine. J Clin Oncol 1998;16:1795–802.
3. Cassidy J, Dirix L, Bisset D et al. A phase I study of capecitabine in combination with oral leucovorin in patients with intractable solid tumors. Clin Cancer Res 1998;4:2755–61.
4. Van Cutsem E, Findlay M, Osterwalder B et al. Capecitabine, an oral fluoropyrimidine carbamate with substantial activity in advanced colorectal cancer: results of a randomized phase II study. J Clin Oncol 2000;18:1337–45.
5. Hoff PM, Ansari R, Batist G et al. Comparison of oral capecitabine (Xeloda®) v intravenous 5-fluorouracil plus leucovorin (Mayo Clinic regimen) as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol (submitted).
6. Van Cutsem E, Twelves C, Cassidy J et al. Oral Xeloda® (capecitabine) compared with intravenous 5-fluorouracil plus leucovorin (Mayo Clinic regimen) in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol (submitted).
Phase IIIb: adjuvant
X-ACT trial

16. Phase III studies of Xeloda® in CRC
Two randomised, open-label, multicentre, phase III trials
Oral Xeloda® versus i.v. 5-FU/leucovorin (LV) (Mayo Clinic regimen) as first-line treatment for advanced and/or metastatic CRC
One study in the Americas, one study in Europe, Israel and Australasia using identical protocols
Treatments
Xeloda®: 1,250mg/m2 twice daily for 14 days followed by a 7-day rest period
Mayo Clinic regimen: LV 20mg/m2 + 5-FU 425mg/m2 days 1–5 every 28 days, i.v. bolus
31. Phase III studies of Xeloda® in CRC
Two randomised, multicentre, open-label, phase III trials were undertaken to compare oral Xeloda® with Mayo Clinic regimen as first-line treatment for metastatic CRC. One trial was conducted in the Americas1 and the other was performed in centres throughout Europe, Australia, New Zealand, Israel and Taiwan.2 The trials used identical protocols.
The primary objective of the studies was to demonstrate that patients receiving oral Xeloda® as first-line treatment for metastatic CRC achieve a response rate at least equivalent to that achieved with Mayo Clinic regimen. Secondary objectives included comparison of efficacy in terms of time to disease progression, overall survival, duration of response and time to first response, and comparison of the safety profile, QoL and medical resource utilisation in the two treatment groups.
Patients were randomised to treatment with either Xeloda® (1,250mg/m2 twice daily for 14 days followed by a 7-day rest period; n=603) or Mayo Clinic regimen (20mg/m2 leucovorin followed by 425mg/m2 5-FU, administered as an i.v. bolus on days 1–5 every 28 days; n=604).
1. Hoff PM, Ansari R, Batist G et al. Comparison of oral capecitabine (Xeloda®) v intravenous 5-fluorouracil plus leucovorin (Mayo Clinic regimen) as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol (submitted).
2. Van Cutsem E, Twelves C, Cassidy J et al. Oral Xeloda® (capecitabine) compared with intravenous 5-fluorouracil plus leucovorin (Mayo Clinic regimen) in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol (submitted).

17. Rationale for integrated analysis
Identical protocols
Identical conduct and monitoring
Protocol pre-defined to pool data
To obtain information on a larger patient population
32. Rationale for integrated analysis
The two phase III trials in CRC were identical in terms of study design, patient selection criteria, conduct and monitoring. Furthermore, the study protocols predefined pooling of all data to obtain information on a large (>1,200) patient population. Therefore, a prospectively designed, integrated analysis of results from the two studies was performed using data from 603 patients treated with Xeloda® and 604 patients treated with Mayo Clinic regimen.1 The results are presented in the following slides.
1. Hoff PM. Capecitabine as first-line treatment for colorectal cancer (CRC): integrated results of 1207 patients (pts) from 2 randomized, phase III studies. On behalf of the Capecitabine CRC Study Group. 25th European Society for Medical Oncology Congress, Hamburg, Germany, October 13–17, 2000 (Abstract 263).

18. Demographics KPS = Karnofsky Performance Score
The demographic characteristics of patients in the two treatment groups were well balanced.1 The median age was 64 years in the Xeloda® group and 63 years in the 5-FU/leucovorin group. The predominant metastatic site was the liver in more than three-quarters of patients in both treatment arms and the lungs in approximately one- third of each group. Approximately one-quarter of patients in both treatment groups had received prior adjuvant treatment.
1. Hoff PM. Capecitabine as first-line treatment for colorectal cancer (CRC): integrated results of 1207 patients (pts) from 2 randomized, phase III studies. On behalf of the Capecitabine CRC Study Group. 25th European Society for Medical Oncology Congress, Hamburg, Germany, October 13–17, 2000 (Abstract 263).
KPS = Karnofsky Performance Score
Hoff PM. Proc ESMO 2000 (Abst 263)

19. Overall tumour response rate
Tumour assessment was performed before the start of treatment and at weeks 6, 12, 18, 24 and 30 by the investigators based on World Health Organization (WHO) criteria. Tumours were also assessed by an Independent Review Committee (IRC) consisting of a panel of radiologists blinded to study treatment, investigator’s assessment and the clinical condition of patients. The IRC used only digitised imaging to assess tumours.
The primary endpoint, response rate, was significantly superior in patients treated with Xeloda® (25.7%) compared with Mayo Clinic regimen (16.7%, p<0.0002).1 The superior efficacy of Xeloda® was confirmed by the IRC-assessed response rate (22.4% vs 13.2%, respectively, p<0.0001).
1. Hoff PM. Capecitabine as first-line treatment for colorectal cancer (CRC): integrated results of 1207 patients (pts) from 2 randomized, phase III studies. On behalf of the Capecitabine CRC Study Group. 25th European Society for Medical Oncology Congress, Hamburg, Germany, October 13–17, 2000 (Abstract 263).
PR = partial response; CR = complete response; IRC = Independent Review Committee
Hoff PM. Proc ESMO 2000 (Abst 263)

20. Response rates by subpopulation
Xeloda® (n=603)
5-FU/LV (n=604) * *
Response rate (%) *
35. Response rates by subpopulation
When response rates were analysed by subpopulation, Xeloda® was found to achieve consistently significantly superior response rates compared with Mayo Clinic regimen.1 A particularly impressive difference was seen in patients who had received prior adjuvant treatment, where the response rate with Xeloda® was 21.1% compared with only 9.0% with Mayo Clinic regimen.
The response rate in patients with metastases predominantly in the liver was 25.6% with Xeloda® and 16.6% with Mayo Clinic regimen. Corresponding values for lung metastases were 33.3% and 10.3%. Xeloda® also resulted in higher response rates in both the subgroup of patients >60 years (26.3% vs 15.0%) and the subgroup of patients £60 years (24.8% vs 19.2%).
1. Hoff PM. Capecitabine as first-line treatment for colorectal cancer (CRC): integrated results of 1207 patients (pts) from 2 randomized, phase III studies. On behalf of the Capecitabine CRC Study Group. 25th European Society for Medical Oncology Congress, Hamburg, Germany, October 13–17, 2000 (Abstract 263). * * *
Prior No prior Liver† Lung† £60 years >60 years
adjuvant adjuvant
*p<0.05
†Predominant site of metastases
Hoff PM. Proc ESMO 2000 (Abst 263)

21. Time to first response Xeloda® (n=603) 5-FU/LV (n=604) Responders (%)
The time of first response in patients who responded to Xeloda® therapy is displayed in 6-week intervals to provide an indication of time to first response. Responses occurred at least as early with Xeloda® compared with Mayo Clinic regimen, and in each time period tumour responses occurred more frequently with Xeloda®.1
1. Hoff PM. Capecitabine as first-line treatment for colorectal cancer (CRC): integrated results of 1207 patients (pts) from 2 randomized, phase III studies. On behalf of the Capecitabine CRC Study Group. 25th European Society for Medical Oncology Congress, Hamburg, Germany, October 13–17, 2000 (Abstract 263).
0–63 64– –147 >147
Study day
Hoff PM. Proc ESMO 2000 (Abst 263)

22. Time to disease progression
Median (CI) Xeloda®: 4.6 (4.3–5.3) 5-FU/LV: 4.7 (4.3–5.4)
Hazard ratio = (0.885–1.123)
Log rank p=0.9535
1.0
0.8
0.6
0.4
0.2
Xeloda® (n=603)
5-FU/LV (n=604)
37. Time to disease progression
Time to disease progression, defined as time from randomisation to progressive disease or death, was equivalent with Xeloda® and Mayo Clinic regimen (median 4.6 months vs 4.7 months, respectively).1 These results were supported by the analysis of time to treatment failure, which included in addition all patients who withdrew from treatment due to adverse events or treatment refusal. The median time to treatment failure was 4.2 months with Xeloda® and 3.6 months with Mayo Clinic regimen.
1. Hoff PM. Capecitabine as first-line treatment for colorectal cancer (CRC): integrated results of 1207 patients (pts) from 2 randomized, phase III studies. On behalf of the Capecitabine CRC Study Group. 25th European Society for Medical Oncology Congress, Hamburg, Germany, October 13–17, 2000 (Abstract 263).
Estimated probability
4.6
4.7
Time (months)
Hoff PM. Proc ESMO 2000 (Abst 263)

23. Overall survival 1.0 0.8 0.6 0.4 0.2 Xeloda® (n=603) 5-FU/LV (n=604)
Xeloda® (n=603)
5-FU/LV (n=604)
Median (CI) Xeloda®: 12.9 (12.0–14.0) 5-FU/LV: 12.9 (11.8–14.0)
Hazard ratio = (0.89–1.14)
Log rank p=0.91
Estimated probability
38. Overall survival
Overall survival was at least equivalent with Xeloda® and Mayo Clinic regimen (median 12.9 months in both groups).1 The hazard ratio was 1.01, with a p value of A multivariate Cox regression analysis confirmed, as expected, that poor KPS, presence of liver metastases, high alkaline phosphatase concentration at baseline and multiple metastatic sites at baseline were prognostic factors for poor survival.
1. Hoff PM. Capecitabine as first-line treatment for colorectal cancer (CRC): integrated results of 1207 patients (pts) from 2 randomized, phase III studies. On behalf of the Capecitabine CRC Study Group. 25th European Society for Medical Oncology Congress, Hamburg, Germany, October 13–17, 2000 (Abstract 263).
12.9
12.9
Time (months)
Hoff PM. Proc ESMO 2000 (Abst 263)

24. Grade 3/4 treatment-related adverse events
Xeloda® (n=596)
5-FU/LV (n=593)
Patients (%)
40. Grade 3/4 treatment-related adverse events
There was a higher incidence of grade 3 and 4 adverse events in the Mayo Clinic regimen group than in the Xeloda® group (396 vs 369 events), and more patients treated with Mayo Clinic regimen experienced grade 4 adverse events (5.1% vs 3.0% with Xeloda®).1 The most common treatment-related grade 3 or 4 adverse event with Mayo Clinic regimen was stomatitis (grade 3: 14.2%; grade 4: 0.5%) compared with 2.0% and 0.2%, respectively, with Xeloda®. Hand-foot syndrome was the most common grade 3 adverse event with Xeloda® (grade 3: 17.1%; grade 4: not applicable), but this could be managed by individual dose titration. Less than two- thirds (61%) of all hand-foot syndrome patients required treatment for grade 3 hand- foot syndrome, with therapy almost always consisting of emollients. In contrast, 89% of patients in the Mayo Clinic regimen group who developed grade 3/4 stomatitis required treatment for this adverse effect. Neutropenic fever and sepsis were significantly more common in the Mayo Clinic regimen group than in patients treated with Xeloda®.
1. Hoff PM. Capecitabine as first-line treatment for colorectal cancer (CRC): integrated results of 1207 patients (pts) from 2 randomized, phase III studies. On behalf of the Capecitabine CRC Study Group. 25th European Society for Medical Oncology Congress, Hamburg, Germany, October 13–17, 2000 (Abstract 263). * * *
Diarrhoea Stomatitis Hand-foot Nausea Vomiting Neutropenic
syndrome fever + sepsis
*p<0.0001
Hoff PM. Proc ESMO 2000 (Abst 263)

25. Most common grade 3/4 laboratory abnormalities
Myelosuppression was very rare with Xeloda®. Grade 3 or 4 neutropenia as a laboratory abnormality was significantly more common with Mayo Clinic regimen than with Xeloda® (21.1% vs 2.2%), resulting in a significantly higher incidence of neutropenic fever and sepsis and more associated hospitalisations.1
Hyperbilirubinaemia (using the strict grading criteria of the old National Cancer Institute of Canada Common Toxicity Criteria [NCIC CTC] scale) occurred more frequently in the Xeloda® group. However, it tended to be an isolated laboratory abnormality affecting primarily the indirect proportion, and was rarely associated with grade 3 or 4 liver transaminase elevations. This effect has been observed in other members of the class and it has been suggested that it is characteristic of oral fluoropyrimidines.
1. Hoff PM. Capecitabine as first-line treatment for colorectal cancer (CRC): integrated results of 1207 patients (pts) from 2 randomized, phase III studies. On behalf of the Capecitabine CRC Study Group. 25th European Society for Medical Oncology Congress, Hamburg, Germany, October 13–17, 2000 (Abstract 263).
NCIC common toxicity criteria; ULN = upper limit of normal
Hoff PM. Proc ESMO 2000 (Abst 263)

26. Hospitalisations for key adverse events
Xeloda® (n=596)
5-FU/LV (n=593) *
No. of patients hospitalised
42. Hospitalisations for key adverse events
Hospitalisation for adverse events was significantly less common with Xeloda® than with Mayo Clinic regimen (76 vs 113 hospitalisations). Similarly, significantly fewer patients receiving Xeloda® were hospitalised (11.6% vs 18.0% with Mayo Clinic regimen).1 Hospitalisation was significantly more common with Mayo Clinic regimen for stomatitis (3.5% vs 0.2%) and neutropenic fever/sepsis (2.9% vs 0.2%). By contrast, hospitalisation for hand-foot syndrome, the most common adverse event with Xeloda® treatment, occurred in only two patients receiving Xeloda®, demonstrating that this localised, cutaneous side effect did not present a major clinical problem. In addition, as an important pharmacoeconomic benefit, fewer consultations/visits were required for treatment administration in the Xeloda® group than in the Mayo Clinic regimen group. The average number of hospital visits for treatment administration during a 12-week period was 15 for Mayo Clinic regimen compared with only four for Xeloda®.
1. Hoff PM. Capecitabine as first-line treatment for colorectal cancer (CRC): integrated results of 1207 patients (pts) from 2 randomized, phase III studies. On behalf of the Capecitabine CRC Study Group. 25th European Society for Medical Oncology Congress, Hamburg, Germany, October 13–17, 2000 (Abstract 263). * *
Overall
Diarrhoea
Vomiting
Stomatitis
Hand-foot syndrome
Infections
Neutropenic fever + sepsis
*p<0.005
Hoff PM. Proc ESMO 2000 (Abst 263)

27. New Combinations Irinotecan+ Xeloda® Oxaliplatin+ Xeloda®
Irinotecan+Oxaliplatin
Irinotecan+Oxaliplatin+ Xeloda®

28. Xeloda® + Oxaliplatin in metastatic colorectal cancer preliminary results of a Swiss study
Xeloda® 2500 mg/m2/d x 14 Oxaliplatin 130 mg/m2 iv day 1 every 3 weeks
patients without prior chemotherapy: response rate ~45%
patients pretreated with 5-FU response rate ~22%
main toxicity: diarrhea

29. Nov, 99
61 years old patient, status post resection of rectal cancer 1 year earlier. Now detection of multiple, inoperable liver metastases. Fig (Nov. 99)

31. After 4 cycles of chemotherapy with Xeloda + Oxaliplatin significant tumor reduction
Fig. 3+4 (March 2000)

33. Beginning of May 2000 right sided hemihepatectomie
Beginning of May 2000 right sided hemihepatectomie. Histologically 3 metastases with extensive (>90%) nekroses.
No extrahepatic metastases.
CT scan 1 week postoperatively

34. CT scan in November 2000: no relapse.

35. Xact-Study
patients: Dukes C colon cancer adjuvant treatment for 6 months
Xeloda® 2500mg/m2/d x 14 every 3 weeks x8
versus
Mayo-regimen x6
5-FU 425mg/m2/d iv+ FA 20mg/m2/d iv, days 1-5, every 4 weeks

36. Xeloda® + Gemcitabine in pancreatic cancer
Treatment regimen
Xeloda® 1300 mg/m2/d orally days in 2 equally divided doses
Gemcitabine 1000mg/m2 iv over 30‘ days 1 and 8
every 3weeks
Result
response rate (PR) ~25%
excellent tolerance

37. Ca 19-9 of patients with initially elevated levels, who received at least 2 complete treatment cycles and had a minimum of 2 measurements. l dose level 1, s level 2, n level 3

38. Liver Metastases of Pancreatic Cancer
Liver Metastases of Pancreatic Cancer. Effect of Chemotherapy with Gemcitabine and Xeloda®
76 years old patient
June 07, September 20, 2000
CA19-9: 451’800 U/ml ’600 U/ml

39. Course of CA 19-9 in a patient with pancreatic cancer
Chemotherapy with Gemcitabine and Xeloda

40. Conclusion
Xeloda® is a valuable new drug for the treatment of advanced colorectal cancer
its major advantages compared to 5-FU+FA are
oral application
faster response
higher response rate
lower toxicity
further advances are to be expected with the
combination of Xeloda® with other new agents
introduction into the adjuvant situation