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D Depisch

Publications and source records attributed to D Depisch.

At least 37 records · Page 2Linked to original sources
PubMed1999

Phase II trial of gemcitabine, epirubicin and granulocyte colony-stimulating factor in patients with advanced pancreatic adenocarcinoma.

Although the novel cytidin analogue gemcitabine has shown superior anti-tumour activity than 5-fluorouracil in advanced pancreatic cancer, further improvements of therapeutic results are warranted. This goal might be achieved by combining gemcitabine with other active drugs. This trial evaluated the efficacy and tolerance of such a combination regimen with epirubicin and granulocyte colony-stimulating factor (G-CSF) in patients with metastatic disease. Seventy patients with metastatic pancreatic adenocarcinoma were enrolled in this multicentre trial. Patients received 4-weekly courses of a combination regimen consisting of epirubicin 60 mg m(-2) given as intravenous bolus injection on day 1, gemcitabine 1000 mg m(-2) infused over 30 min on days 1, 8 and 15, and G-CSF administered at 5 microg kg(-1) day(-1) subcutaneously from days 2-6 during each cycle. The efficacy of treatment was assessed by conventional measures, i.e. objective response, progression-free and overall survival, as well as by analysis of clinical benefit response (defined as > or = 50% reduction in pain intensity, > or = 50% reduction in daily analgesic consumption, and/or > or = 20-point improvement in Karnofsky performance status that was sustained for > or = 4 consecutive weeks). Of 66 patients evaluable for objective response, one achieved complete and 13 partial remissions, for an overall response rate of 21% (95% confidence interval (CI), 12-33%); 27 additional patients (41%) had stable and 25 (38%) increasing disease. The median time to progression was 3.8 months. Median survival was 7.8 months, and the probability of surviving beyond 12 months was 21.2%. Out of 60 patients with tumour-related symptoms, who were considered evaluable for clinical benefit response, 26 (43%) experienced significant palliation. The median time to achieve a clinical benefit response was 7 weeks, and its median duration was 22 weeks. Chemotherapy was well-tolerated with leukopenia/granulocytopenia representing the most common and dose-limiting side-effect. Gastrointestinal and other subjective toxicities were infrequent and generally rated minor. We conclude that the combination of gemcitabine, epirubicin and G-CSF seems to be an effective palliative treatment with only moderate toxic effects in patients with metastatic pancreatic adenocarcinoma. Our results in terms of objective and clinical benefit response, as well as survival seem to suggest an advantage over gemcitabine-monotherapy, though this remains to be confirmed in a randomized trial.

Adenocarcinoma↗
PubMed1999

Combined irinotecan and oxaliplatin plus granulocyte colony-stimulating factor in patients with advanced fluoropyrimidine/leucovorin-pretreated colorectal cancer.

PURPOSE: To evaluate the efficacy and tolerance of combined irinotecan and oxaliplatin in patients with advanced colorectal cancer pretreated with leucovorin-modulated fluoropyrimidines. PATIENTS AND METHODS: Thirty-six patients with metastatic colorectal cancer, who progressed while receiving or within 6 months after discontinuing palliative chemotherapy with fluoropyrimidines/leucovorin, were enrolled onto this study. Treatment consisted of oxaliplatin 85 mg/m2 on days 1 + 15 and irinotecan 80 mg/m2 on days 1 + 8 + 15 every 4 weeks. Depending on the absolute neutrophil counts (ANC) on the day of scheduled chemotherapeutic drug administration, a 5-day course of granulocyte colony-stimulating factor (G-CSF) 5 microg/kg/d was given. RESULTS: The overall response rate was 42% for all 36 assessable patients (95% confidence interval, 26% to 59%), including two complete remissions (6%). Thirteen additional patients (36%) had stable disease, and only eight (22%) progressed. The median time to treatment failure was 7.5 months (range, 1 to 13.5+ months). After a median follow-up time of 14 months, 19 patients (53%) are still alive. Hematologic toxicity was commonly observed, although according to the ANC-adapted use of G-CSF (in 31 patients during 81 of 174 courses), it was generally mild: grade 3 and 4 granulocytopenia occurred in only five and two cases, respectively. The most frequent nonhematologic adverse reactions were nausea/emesis and diarrhea, which were rated severe in 17% and 19%, respectively. CONCLUSION: Our data suggest that the combination of irinotecan and oxaliplatin with or without G-CSF has substantial antitumor activity in patients with progressive fluoropyrimidine/leucovorin-pretreated colorectal cancer. Overall toxicity was modest, with gastrointestinal symptoms constituting the dose-limiting side effects. Further evaluation of this regimen seems warranted.

Adult↗
PubMed1998

Combined intravenous and intraperitoneal chemotherapy with fluorouracil + leucovorin vs fluorouracil + levamisole for adjuvant therapy of resected colon carcinoma.

Adjuvant chemotherapy with fluorouracil (FU) and levamisole or FU/leucovorin (LV) has been established as effective adjuvant treatment for patients with stage III colon cancer. Among several other promising treatment strategies in resected colon cancer, intraperitoneal anti-cancer drug administration with its appealing rationale of counteracting microscopic residual disease on peritoneal surfaces and occult metachronous liver metastases by achieving high intraportal drug concentrations has not yet undergone sufficient clinical evaluation. To determine whether a combination of this locoregional therapeutic concept with systemic intravenous administration of FU/LV would yield better results than conventional adjuvant chemoimmunotherapy with FU/levamisole, the present randomized study was initiated. A total of 241 patients with resected stage III or high-risk stage II (T4N0M0) colon cancer were randomly assigned to 'standard therapy' with FU and levamisole, given for a duration of 6 months, or to an investigational arm, consisting of LV 200 mg m(-2) plus FU 350 mg m(-2), both administered intravenously (days 1-4) and intraperitoneally (days 1 and 3) every 4 weeks for a total of six courses. In patients with stage II disease, no significant difference was noted between the two arms after a median follow-up time of 4 years (range 2.5-6 years). Among 196 eligible patients with stage III disease, however, a comparative analysis of the two treatment groups suggested both an improvement in disease-free survival (P = 0.0014) and a survival advantage (P = 0.0005), with an estimated 43% reduction in mortality rate (95% confidence interval 26-70%) in favour of the investigational arm. In agreement with its theoretical rationale, combined intraperitoneal and intravenous FU/LV was particularly effective in reducing locoregional tumour recurrences with or without liver or other organ site involvement (9 vs 25 patients in the FU/levamisole arm; P = 0.005). Treatment-associated side-effects were infrequent and generally mild in both arms, although a lower rate of severe (WHO grade 3) adverse reactions was noted in patients receiving locoregional plus intravenous chemotherapy (3% vs 12%; P = 0.01). The results of this trial suggest that combined intraperitoneal plus systemic intravenous chemotherapy with FU/LV is a promising adjuvant treatment strategy in patients with surgically resected stage III colon carcinoma.

Adenocarcinoma↗
PubMed1998

Effective treatment of advanced breast cancer with vinorelbine, 5-fluorouracil and l-leucovorin plus human granulocyte colony-stimulating factor.

A phase II trial was performed to investigate the efficacy and tolerance of vinorelbine (VNB), 5-fluorouracil (5-FU), l-leucovorin (LLV) and recombinant human granulocyte colony-stimulating factor (G-CSF) in advanced breast cancer. Between August 1994 and October 1996, 53 patients entered this trial. Thirty-seven patients were previously untreated and 16 patients had failed previous palliative chemotherapy with (n = 12) or without anthracyclines (n = 4). Therapy consisted of VNB 40 mg m(-2) diluted in 250 ml of saline infused over 30 min on days 1 and 14 and LLV 100 mg m(-2) administered by intravenous bolus injection and 5-FU 400 mg m(-2) diluted in 500 ml of saline infused over 2 h, both given on days 1-5 every 4 weeks. G-CSF was administered at 5 microg kg(-1) day(-1) subcutaneously on days 6-10 during each cycle. Treatment was continued in cases of response or stable disease until a total of six courses were completed. The overall response rate was 59% for chemotherapeutically naive patients (95% confidence interval 42-75%), including five complete responses (CR; 13%) and 17 partial responses (PR; 46%); ten patients (27%) had stable disease (SD) and only five (14%) progressed (PD). Second-line chemotherapy with this regimen resulted in 3/16 (19%) objective remissions, but nine patients had SD and four had PD. The median time to progression was 10.5 months (range 2-23) in previously untreated patients and 7.0 months (range 2-19) in those who had failed prior chemotherapy. After a median follow-up time of 14 months, 29 patients (55%) are still alive with metastatic disease; median survival has not been reached yet. The dose-limiting toxicity was myelosuppression: WHO grade III and IV neutropenia occurred in 15 (28%) and four patients (8%), and was complicated by septicaemia in two; grade III anaemia and thrombocytopenia were noted in four (8%) and three (6%) patients respectively. Severe (WHO grade 3) non-haematological toxicities included stomatitis in 6% and nausea/vomiting and alopecia in 2% each. Our data suggest that the combination of vinorelbine, 5-fluorouracil and l-leucovorin plus G-CSF is an effective first line regimen for treatment of advanced breast cancer. Overall toxicity was modest, with myelosuppression being the dose-limiting side-effect. Other severe adverse reactions were uncommon.

Adult↗
PubMed1998

Reinduction therapy with the same cytostatic regimen in patients with advanced colorectal cancer.

The aim of the study was to investigate the therapeutic value of reinduction therapy with the same cytostatic treatment that had been used for induction treatment in patients with metastatic colorectal cancer. A total of 71 patients, all of whom had responded or achieved stable disease lasting > or = 12 weeks after six monthly courses of first-line treatment with 5-fluorouracil + racemic leucovorin (5-FU/LV; n = 35) or 5-FU plus the l-isomer of LV (LLV; n = 34) were entered in this study. At the time of relapse, the same treatment was used for initial therapy: racemic LV or LLV was administered at 100 mg m(-2) day(-1) by i.v. bolus injection, immediately followed by 5-FU 400 mg m(-2) day(-1) given as a 2-h infusion. Chemotherapeutic drugs were given on 5 consecutive days at 4-week intervals x 6 or until there was evidence of tumour progression. Among 49 evaluable patients, reinduction therapy that was initiated after a median treatment-free interval of 5.4 months (range 3-14.5) resulted in nine partial response (PR) (18%) and 26 stable disease (SD) (53%), yielding an overall tumour control rate of 69% (95% confidence interval, 54.6-81.7%). The median time to treatment failure from reinduction was 6.4 months, and the median survival duration from reinduction was 8.9 months (20.1 months as judged from the beginning of induction therapy). The toxicity associated with retreatment was generally mild to moderate; compared with initial treatment, there was no significant difference in terms of the overall rate (P = 0.33) or severity (P = 0.19) of adverse reactions. Our data suggest that in patients with advanced colorectal cancer an interrupted treatment strategy, i.e. retreatment with the same regimen in case of relapse > or = 3 months after discontinuation of 6 months of successful treatment with 5-FU/LV or 5-FU/LLV is an acceptable therapeutic concept.

Adult↗
PubMed1997

MDR1 RNA transcripts do not indicate long-term prognosis in colorectal carcinomas.

Because P-glycoprotein expression might be associated with a more aggressive behaviour of colorectal carcinomas (Weinstein et al., Cancer Res, 1991, 51, 2720-2726), we determined the relationship between MDR1 RNA expression of the carcinomas and the survival of the patients. At a median duration of follow-up of 86 months, event-free survival of patients with MDR1 RNA-negative tumours (n = 35) was not significantly different to that of patients with MDR1 RNA positive tumours (n = 67). Among the different tumour stages, event-free survival of the patients was also independent of MDR1 gene expression of the tumours. Thus, these findings do not support the hypothesis that local aggressiveness of P-glycoprotein positive tumour cells translates into worse clinical outcome.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Expression of the multidrug resistance-associated protein (MRP) gene in colorectal carcinomas.

To determine the clinical significance of MRP in patients with colorectal carcinomas, we have studied the expression of the MRP gene by reverse transcription-polymerase chain reaction (RT-PCR) (n = 105) and by immunohistochemistry (n = 30). MRP mRNA expression was observed in 92 (88%) tumour specimens. Positive MRP staining with monoclonal antibodies QCRL-1 and QCRL-3 was detected in all samples studied with strong staining in seven (23%) and weak staining in 23 (77%) specimens. Strong MRP staining in these samples did not appear to be related to the age and sex of the patients, localization of the primary tumour, histological grade, tumour size, lymph node metastasis, distant metastasis and tumour stage. Strong MRP staining was not associated with MDR1 RNA or P-glycoprotein (P-gp) expression. Kaplan-Meier curves revealed that overall survival of patients with strong MRP-staining tumours was similar to the survival of patients with weak-staining tumours. These data indicate that the MRP gene is expressed in primary colorectal carcinomas but is neither related to known prognostic factors nor a prognostic factor by itself.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Fluorouracil plus racemic leucovorin versus fluorouracil combined with the pure l-isomer of leucovorin for the treatment of advanced colorectal cancer: a randomized phase III study.

PURPOSE: To compare the efficacy and toxicity of fluorouracil (FU) and racemic leucovorin (d,l-LV) versus FU combined with the l-isomer of leucovorin (l-LV) in the treatment of advanced colorectal cancer. PATIENTS AND METHODS: A total of 248 patients with advanced measurable colorectal cancer previously unexposed to chemotherapy were randomly assigned to treatment with either FU (400 mg/m2/d by intravenous [I.V.] infusion for 2 hours) and racemic LV (100 mg/m2/d by I.V. bolus injection) given for 5 consecutive days, or the combination of FU and the pure l-isomer of LV using the same dose schedule. In both treatment arms, courses were administered every 28 days if toxicity allowed for a total of 6 months, unless evidence of tumor progression was documented earlier. RESULTS: There were no significant differences between the FU/racemic LV and the FU/l-LV arm in the overall response rate (25% v 32%), duration of response (7.2 v 8.0 months), median time to progression or death (6.25 v 8.0 months), or median overall survival time (14.5 v 15.0 months). Except for minor myeloid toxic effects associated with FU/l-LV, there was also no significant difference in terms of adverse reactions. Gastrointestinal symptoms, specifically mucasitis and diarrhea, were less frequent and less severe in both treatment arms compared with other trials with FU/racemic LV reported in the literature, which might be because of the prolonged administration of FU used in both arms. CONCLUSION: The combination of FU/l-LV produced response rates, response durations, and survival times similar to those with FU/d,l-LV. Biochemical modulation of FU by either pure l-LV or racemic LV thus appears to result in equivalent clinical efficacy.

Adult↗
PubMed1996

Effective treatment of advanced breast cancer with vinorelbine, mitomycin C plus human granulocyte colony-stimulating factor.

A phase II trial was performed to evaluate the efficacy and tolerance of vinorelbine (VNB), mitomycin C (MMC), and recombinant human granulocyte colony-stimulating factor (G-CSF) in advanced breast cancer. Between October 1992 and July 1994, 55 patients entered this trial. Nine patients had locally advanced disease and 46 had distant metastases, including 14 who had received previous palliative chemotherapy with (n = 9) or without anthracyclines (n = 5). Therapy consisted of VNB 40-50 mg m(-2) diluted in 250 ml saline infused over 30 min every 3 weeks, and MMC 15 mg m(-2) administered by intravenous bolus injection every 6 weeks. G-CSF was given at 5 microg kg(-1) day(-1) subcutaneously from days 2 to 7 following each cytotoxic drug administration. Treatment was continued in case of response or stable disease for a total of six courses. The overall response rate was 73% for all 55 patients (95% confidence interval, 59-84%), including 12 (22%) complete response (CR) and 28 (51%) partial response (PR); 13 patients (24%) had stable disease (SD), and only two (4%) progressed. All nine patients with locally advanced disease were rated responsive (two pCR, seven PR) and underwent surgery with curative intent. Eight out of nine remain disease free after a median observation period of 18 months (range, 13.5-28 months). Among the 32 previously untreated patients with metastatic disease, nine (28%) achieved CR, 15 PR (47%), seven SD (22%) and one PD (3%). Second-line chemotherapy with this regimen resulted in 7/14 (50%) objective remissions (one CR, six PR), six had SD and one PD. The median time to progression was 12 months (range, 2-24+ months) in previously untreated patients with disseminated disease, and 6.0 months (range, 2-22 months) in those who had failed prior chemotherapy. After a median follow-up time of 20 months, 24 patients with distant metastases are still alive with disease; median survival has not been reached yet. The dose-limiting toxicity was myelosuppression: six (11%) and ten patients (18%) had World Health Organization grade 3, and eight (14%) and nine patients (16%) had grade 4 leucopenia and granulocytopenia respectively. Severe (WHO grade 3) non-haematological toxicities included nausea/vomiting in 7%, constipation in 9%, peripheral neuropathy in 5%, infectious episodes in 7%, phlebitis due to drug extravasation in 5%, alopecia in 9%, and acute reversible pulmonary toxicity in 11%. Our data suggest that vinorelbine, mitomycin C plus G-CSF has an excellent anti-tumour activity in advanced breast cancer, probably superior to most other available combination chemotherapy regimens. This combination does not seem to present significant cross-resistance with previous CMF or anthracycline regimens. Apart from reversible, acute pulmonary toxicity, a rare adverse reaction that had previously been described for VNB, as well as the combination of natural vinca alkaloids with mitomycin C, and few episodes of grade 3 neurotoxicity (all of which occurred at the initial 50 mg m(-2) VNB dose level), the tolerance of this regimen seems acceptable and justifies further evaluation in front-line and salvage therapy of advanced breast cancer.

Adult↗
PubMed1996

MRP and MDR1 gene expression in primary breast carcinomas.

To evaluate the clinically important mechanisms of drug resistance in breast cancer, the expression of the MRP gene and the corresponding one for the MDR1 gene were determined in primary breast carcinoma specimens by both reverse transcription-PCR (n = 134) and immunohistochemistry (n = 63). Expression of MRP RNA was observed in all breast cancer specimens. MDR1 RNA was detected in 80 (60%) of the carcinomas. Staining with monoclonal antibodies QCRL-1 and QCRL-3, which both recognize MRP, was strong in 15 (24%) and weak in the remaining 48 specimens (76%). Staining with C219, which recognizes P-glycoprotein, was strong in 6 (9%), weak in 30 (48%), and negative in 27 (43%) of the samples. Strong MRP staining was more frequent in T3 and T4 tumors than in T1 and T2 tumors and in the primary tumors of patients with distant metastases but was independent of age, menopausal status, histology, histological grade, estrogen receptor, progesterone receptor, and lymph node involvement. No correlation between MRP staining and expression of MDR1 RNA or P-glycoprotein was observed. Thus, these results indicate expression of both the MRP gene and the MDR1 gene in primary breast carcinomas and suggest that clinical drug resistance in breast cancer is most likely multifactorial.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Combined intraperitoneal plus intravenous chemotherapy after curative resection for colonic adenocarcinoma.

Patients who underwent potential curative surgery for colonic adenocarcinoma were enrolled in a prospectively randomised, controlled clinical trial of combined intraperitoneal (i.p.) plus systemic intravenous (i.v.) chemotherapy with 5-fluorouracil (5-FU) and leucovorin (LV). We investigated whether this adjuvant treatment approach, specifically addressing the risk of peritoneal and hepatic recurrence, could improve disease-free and overall survival. Between May 1988 and December 1990, 121 patients with resected stage III or high-risk stage II (T4N0M0) colon cancer were randomly assigned for observation (which was considered standard care until the NIH consensus conference) or adjuvant chemotherapy with LV (200 mg/m2) plus 5-FU (350 mg/m2), both given i.v. (days 1-4) and i.p. (days 1 and 3) every 4 weeks for a total of six courses. After a median follow-up time of 4.6 years, a comparative analysis between the two groups of patients suggested both an improvement in disease-free survival (75% versus 58%; P = 0.06) and a survival advantage (78% versus 63%; P = 0.05) in favour of adjuvant chemotherapy. The sites of recurrence were also different, i.e. local regional and intrahepatic tumour recurrences were observed in only 6/58 (10%) and 5/58 (9%) adjuvant treated patients as compared to 11/60 (18%) and 10/60 (17%) observed patients. The overall benefit of adjuvant therapy appeared to be greatest in patients with stage III colon cancer. Treatment-associated toxicity was infrequent and generally mild with only 5% experiencing severe (WHO grade 3) adverse reactions. Interim results of this adjuvant trial suggest that combined i.p. plus systemic i.v. chemotherapy with 5-FU and LV represents a potentially effective adjuvant regimen in stage II/III colon cancer.

Adenocarcinoma↗
PubMed1994

Randomized comparison of fluorouracil and leucovorin therapy versus fluorouracil, leucovorin, and cisplatin therapy in patients with advanced colorectal cancer.

BACKGROUND: Because of experimental and preliminary clinical evidence that additional modulation of the biochemical pharmacology and cytotoxicity of 5-fluorouracil (5-FU) and leucovorin (LV) may be possible by combination of these agents with cisplatin (CDDP), the authors undertook a prospective randomized trial in patients with colorectal cancer. METHODS: Between 1989 and 1992, 138 patients with advanced measurable colorectal cancer previously unexposed to chemotherapy were randomly assigned to treatment with either 5-FU (425 mg/m2) and LV (20 mg/m2) for 5 days, or the combination of 5-FU and LV in the same daily dose plus cisplatin (20 mg/m2), each drug given for 4 consecutive days. In both treatment arms, courses were administered every 28 days, if toxicity allowed, for a total of 6 months or until evidence of tumor progression. RESULTS: The overall responses (complete and partial response) were 19% and 28% for the 5-FU/LV and the 5-FU/LV/CDDP treatment arms, respectively. Although the three-drug combination appeared superior to 5-FU/LV for time to progression or death (8.5 versus 5.2 months; P = 0.042), there was no evidence that the adoption of cisplatin will translate into a definite survival advantage. A comparative analysis of the toxicities experienced by the patients in the two treatment groups showed a comparable rate, although severe side effects (P < 0.05), specifically stomatitis (P = 0.013), were noticed more frequently in patients treated with 5-FU/LV for 5 days. CONCLUSIONS: These results suggest that the therapeutic index of 5-FU/LV in metastatic colorectal cancer may be improved with the addition of cisplatin. However, the somewhat better therapeutic activity and lower incidence of severe gastrointestinal side effects have to be weighed against additional pharmaceutical charges and the need for a more intense antiemetic regimen.

Adult↗
PubMed1994

Amonafide as first-line chemotherapy for metastatic breast cancer.

In a phase II study, 32 patients with advanced breast cancer previously unexposed to palliative cytotoxic chemotherapy were treated with amonafide, 800-900 mg intravenously over 3 h repeated every 4 weeks. Objective response was seen in 8 patients including 1 complete response, 10 patients had stable disease and 14 patients progressed so the overall response was 25% (95% confidence interval, 11-43%). The most frequently encountered side-effects were haematological (granulocytopenia > or = WHO grade 3 was encountered in 7/24 patients at 800 mg/m2 and in 3/8 patients at 900 mg/m2 amonafide) and nausea/vomiting (62%), despite prophylactic use of ondansetron. Non-haematological severe adverse reactions included neurotoxicity WHO grade 3 in 1 patient and orthostatic hypotension WHO grade 4 in another. In summary, the results of this trial suggest a limited therapeutic index of amonafide if used at this dose with this administration schedule.

Adenine↗
PubMed1994

Adjuvant intraperitoneal cisplatin chemotherapy does not improve long-term survival after surgery for advanced gastric cancer.

PURPOSE: The long-term survival probability of patients who undergo surgery for stage 3 and 4 gastric cancer is poor, predominantly due to metastatic spread of the tumor. Depending on the type of tumor histology, the pathway of metastases is mainly peritoneal or hepatic dissemination. Interruption of this mechanism may be possible by intraperitoneal chemotherapy (IPT). PATIENTS AND METHODS: In a prospective randomized trial of 67 patients undergoing surgery for stage 3 and 4 gastric cancer, 33 patients underwent adjuvant postoperative IPT with cisplatin, while 34 control subjects remained untreated. RESULTS: Patients in the treatment group received a median of four IPT perfusions. Apart from frequent nausea, no adverse reactions or complications were noted. The median disease-free survival durations were 12.7 months and 9.7 months in treated patients and controls, respectively (P = .8). After a median follow-up duration of 72 months, 54 patients (80%) had died of primary disease or related complications. The median survival duration for IPT patients was 17.3 months as compared with 16.0 months for controls (P = .6). Autopsies were performed on 12 (18%) of 54 patients who died, and showed tumor spread to the peritoneal cavity and/or to the liver, irrespective of the application of IPT. CONCLUSION: IPT with cisplatin monotherapy does not improve survival probability after surgery for stage 3 and 4 gastric cancer. The reasons for ineffectiveness of IPT may be the choice of an unsuitable chemotherapeutic agent, an inefficient modus of application, or a lack of sufficient drug penetration into the serosa or peritoneal metastasis.

Aged↗
PubMed1993

A phase I-II study of epirubicin, 5-fluorouracil, and leucovorin in advanced adenocarcinoma of the stomach.

BACKGROUND: To determine the maximum tolerated dose of epirubicin for use in combination with 5-fluorouracil (5-FU) and low-dose leucovorin (LV), a Phase I-II trial was conducted in 37 patients with advanced gastric carcinoma. METHODS: The doses of 5-FU (425 mg/m2) and LV (20 mg/m2), both given intravenously on days 1-5, were held constant while the dose of epirubicin was escalated in cohorts of patients (beginning dose, 50 mg/m2 on day 1). Cycles were repeated every 4 weeks. RESULTS: Significant gastrointestinal symptoms and myelosuppression were observed infrequently at the initial dose level. At a dose of 60 mg/m2 of epirubicin on day 1, however, five of eight patients had significant mucosal toxic effects during the first cycle of therapy. In addition, two patients treated at this dose level had Grade 4 granulocytopenia with insufficient recovery to permit a second course by day 28, and one patient each had severe diarrhea and nausea and vomiting. Among 37 patients with assessable disease, there were 3 complete and 11 partial responses (response rate, 38%). CONCLUSIONS: LV modulation of 5-FU can be incorporated safely into combination chemotherapy with epirubicin and provides a relatively active regimen for treatment of disseminated gastric cancer.

Adenocarcinoma↗
PubMed1993

Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer.

OBJECTIVES: To compare the length of survival and quality of life in patients given combination chemotherapy in addition to supportive care and in patients given only supportive care. DESIGN: Randomised study. SETTING: Gastrointestinal oncology departments. PATIENTS: 40 previously untreated patients with histologically confirmed, measurable colorectal cancer that was locally recurrent or metastatic. INTERVENTIONS: Patients were allocated randomly to receive chemotherapy or only supportive care in a ratio of 2:1 according to performance status, metastatic disease of the liver, and weight loss in the six months before entering the study. Chemotherapy consisted of four week cycles of intravenous leucovorin (200 mg/m2/day) followed by 5-fluorouracil (550 mg/m2/day) and cisplatin (20 mg/m2/day), each drug being given on the first four days of the cycle. MAIN OUTCOME MEASURES: Length of survival and quality of life score with an optimised functional living index-cancer scale. RESULTS: Overall survival was significantly longer for patients given chemotherapy (11.0 months) than for those receiving supportive care alone (5.0 months; p = 0.006). Despite common association of chemotherapy with mild to moderate gastrointestinal symptoms, there was no significant difference between the two groups in global or subgroup quality of life scores. In patients with abnormal scores before treatment, quality of life seemed better in the chemotherapy arm. CONCLUSIONS: In this sample of patients with disseminated colorectal cancer the chemotherapy regimen was an effective form of palliative treatment.

Adenocarcinoma↗
PubMed1993

MDR1 gene expression and its clinical relevance in primary gastric carcinomas.

BACKGROUND: Drug resistance remains a major problem in gastric carcinomas. To evaluate the mechanisms involved in this resistance, the authors determined the expression of the MDR1 gene, a multidrug resistance gene, in primary gastric carcinomas. METHODS: MDR1 RNA levels of gastric carcinoma specimens (n = 22) were determined by slot blot analysis. An MDR1 cDNA (probe 5A) was used for the hybridization. RESULTS: MDR1 RNA was detected in 41% of the gastric carcinomas, with high levels in 18% of the specimens. No expression of the MDR3 gene was observed in these tumors. MDR1 gene expression was independent of patient age, tumor localization, and lymph node involvement. However, MDR1 RNA expression was less frequent in locally advanced tumors and was absent in the primary tumors of all six patients who had distant metastases. CONCLUSIONS: The data indicate that multidrug-resistant cells are present in primary gastric carcinomas and suggest that multidrug resistance might contribute to the clinical drug resistance of these tumors.

Adenocarcinoma↗