Biomedical subjects

W Scheithauer

Publications and source records attributed to W Scheithauer.

At least 55 records · Page 3Linked to original sources

PubMed2001

Treatment of advanced hepatocellular carcinoma with biweekly high-dose gemcitabine.

INTRODUCTION: Until today, an optimal palliative treatment regimen has not been defined for patients with advanced hepatocellular carcinoma. Since the novel cytidine analog gemcitabine has shown strong antitumor effects in vitro in a human hepatoma cell line and its therapeutic potential seems well established in several different tumors including gastrointestinal adenocarcinomas, the present phase II trial using a dose-intensified biweekly administration schedule was initiated. PATIENTS AND METHODS: 17 patients with histologically confirmed unresectable advanced or metastatic hepatoma were treated with gemcitabine 2,200 mg/m(2) given as a 30-min intravenous infusion on days 1 and 15. Treatment courses were repeated every 4 weeks. RESULTS: All patients were evaluable for response and toxicity assessment. No objective response was achieved, stable disease occurred in 8 patients (47%), and 9 progressed while on chemotherapy. The median time to progression was 4 months (range 1.5-14 months), and the median survival time was 8.5 months (range 2.5-16.0+ months). Treatment was well tolerated with mild or moderate leukopenia, thrombocytopenia and anemia representing the most common side effects. Gastrointestinal and other subjective toxicities were infrequent and also generally mild. CONCLUSIONS: In view of the disappointing treatment results, gemcitabine using this particular dose regimen should not be considered for further investigation in patients with advanced hepatocellular carcinoma.

Adult↗

PubMed2001

Answering patients' needs: oral alternatives to intravenous therapy.

Metastatic colorectal cancer has traditionally been treated with i.v. 5-fluorouracil (5-FU), with or without leucovorin (LV). 5-FU is administered as either an i.v. bolus or a protracted infusion. Although schedules using the latter method offer efficacy benefits (objective response rate, time to disease progression), protracted infusion schedules are often associated with medical complications, inconvenience, high costs, and poor quality of life. Issues such as quality of life and convenience have influenced treatment decisions, but the availability of oral fluoropyrimidines represents a new development in this domain. Studies have confirmed that the majority of patients prefer oral to i.v. chemotherapy. Questionnaire-based studies have also demonstrated a preference for home-based rather than hospital-/clinic-based therapy. This preference was one of the driving forces behind the development of the oral fluoropyrimidines capecitabine (Xeloda) and uracil plus tegafur (UFT). Oral agents offer patients a more convenient treatment option that can be administered at home, providing patients with a greater sense of control over their therapy, while avoiding the medical complications and psychological distress associated with venous access. This article highlights some of the problems associated with i.v. therapy and reviews the available data on patient preference, including results of a recent, randomized, phase II study. It also provides a critical evaluation of the efficacy and safety profiles of the only two oral fluoropyrimidines approved for prescription, capecitabine and UFT/LV (UFT/LV not available in Germany and the U.S.), compared with those of two infused, 5-FU-based regimens. Finally, the results of an interactive debate exploring the opinions of approximately 400 oncologists on the issues of oral versus i.v. therapy are presented.

Administration, Oral↗

PubMed2000

Fatal liver failure after the administration of raltitrexed for cancer chemotherapy: a report of two cases.

BACKGROUND: Acute fatal liver failure is a relatively rare event after the administration of antineoplastic drugs. To the authors' knowledge, there have been no published reports of this phenomenon after the administration of the widely applied cytotoxic agent raltitrexed. METHODS: The authors present two cases of fulminant fatal liver failure that occurred after the administration of raltitrexed as anticancer chemotherapy. RESULTS: A female patient age 76 years and a male patient age 56 years were given raltitrexed as adjuvant treatment of colorectal carcinoma and as palliative therapy for advanced biliary carcinoma, respectively. Although the initial cycles of chemotherapy were uneventful, both patients developed fulminant liver failure with rapid deterioration of their condition after the second and sixth cycles of chemotherapy, respectively, and both died within 24 hours despite immediate hospitalization. Histologic evaluation of liver samples taken during autopsy showed signs of acute necrosis involving roughly 50% of the liver without signs of subacute liver toxicity. CONCLUSIONS: To the authors' knowledge the current study is the first to demonstrate fatal liver toxicity after chemotherapy with the thymidylate synthase inhibitor raltitrexed. Clinicians should be aware of the potential acute fatal side effect of this otherwise well tolerated and widely used cytotoxic agent.

Aged↗

PubMed2000

Treatment of patients with advanced nonsmall cell lung carcinoma using docetaxel and gemcitabine plus granulocyte-colony stimulating factor.

BACKGROUND: A combination regimen comprised of docetaxel, gemcitabine, and granulocyte-colony stimulating factor (G-CSF) was studied in patients with advanced nonsmall cell lung carcinoma (NSCLC) to determine its antitumor efficacy and tolerance. METHODS: Thirty-four patients with advanced measurable NSCLC (3 patients with Stage IIIB and 31 patients with Stage IV disease) were treated with an intravenous combination chemotherapy regimen comprised of docetaxel, 80 mg/m(2), on Day 1 and gemcitabine, 1000 mg/m(2), on Days 1 and 10; G-CSF, 5 microg/kg, was administered subcutaneously between Days 2 and 8. Treatment cycles were repeated every 3 weeks. All patients were evaluable for toxicity and response assessment. A total of 163 courses was administered. RESULTS: Objective tumor response was noted in 17 patients (50%; 95% confidence interval, 32. 5-67.5%), including 2 complete responses (6%) and 15 partial responses (44%). There was no change in 10 patients (29%) and 7 patients developed progressive disease. The median duration of response was 6.5 months (range, 3-15 months) and the median time to disease progression for all patients was 6.8 months (range, 1.8-18 months). The median overall survival time was 13.0 months (range, 2. 5-23+ months) with a 1-year survival rate of 55.8%. Myelosuppression was the most frequently encountered adverse reaction, although World Health Organization Grade 3 or 4 leukocytopenia and/or granulocytopenia occurred in only 18% and 24% of patients, respectively. Other toxicities generally were mild to moderate, and always fully reversible. CONCLUSIONS: With a response rate of 50% and a median survival time of 13 months, the drug combination described in the current study appears to have significant activity against advanced metastatic NSCLC. Due to its fairly good tolerance and ease of administration, further investigation of this regimen appears warranted.

Adult↗

PubMed2000

A phase II trial of biweekly high dose gemcitabine for patients with metastatic pancreatic adenocarcinoma.

BACKGROUND: Although the novel cytidine analog gemcitabine has shown superior antitumor activity compared with weekly bolus 5-fluorouracil in patients with advanced pancreatic carcinoma, further improvements of therapeutic results are warranted. The current Phase II study was initiated to investigate whether this might be achieved by dose intensification. METHODS: Between August 1997 and September 1998, 43 consecutive patients with metastatic pancreatic adenocarcinoma were enrolled in this multicenter Phase II trial. Patients received 4 weekly courses of gemcitabine 2200 mg/m((2)) given as intravenous infusion during 30 minutes on Days 1 and 15 for a duration of 6 months unless there was prior evidence of progressive disease. The efficacy of treatment was assessed according to standard criteria, i.e., objective response, progression free survival, and overall survival, as well as by analysis of clinical benefit response (defined as >/= 50% reduction in pain intensity, >/= 50% reduction in daily analgesic consumption, and/or >/= 20 point improvement in Karnofsky performance status that was sustained for >/= 4 consecutive weeks). RESULTS: Of 43 patients evaluable for objective response, 1 achieved complete and 8 partial remissions, for an overall response rate of 21% (95% confidence interval, 10-36%); 18 additional patients (42%) had stable and 16 (37%) progressive disease. The median time to progression was 5.3 months. Median survival was 8.8 months, and the probability of surviving beyond 12 months was 26.3%. Of 36 patients with tumor-related symptoms who were considered evaluable for clinical benefit response, 16 (44%) experienced significant palliation. The median time to achieve a clinical benefit response was 6 weeks, and its median duration was 27 weeks. Chemotherapy was well tolerated, with leukopenia/granulocytopenia representing the most common side effect. Gastrointestinal and other subjective toxicities were infrequent and generally mild. CONCLUSIONS: Biweekly high dose gemcitabine seems to represent a safe, tolerable, and effective regimen for the palliative treatment of patients with advanced pancreatic carcinoma.

Adenocarcinoma↗

PubMed2000

Chemotherapy for the treatment of patients with primary high grade gastric B-cell lymphoma of modified Ann Arbor Stages IE and IIE.

BACKGROUND: Surgical intervention and combined modality treatment including radiation and chemotherapy have been studied widely in patients with high grade gastric B-cell lymphoma, whereas to the authors' knowledge the role of chemotherapy alone in patients with localized disease has not been investigated extensively. METHODS: Twenty-five consecutive patients with primary high grade gastric B-cell lymphoma of localized modified Ann Arbor Stages IE and IIE were studied prospectively at the study institution. Patients age < 75 years (n = 17; age range, 41-75 years) were given a standard regimen comprised of doxorubicin, cyclophosphamide, vincristine, and prednisone (CHOP), whereas patients age > 75 years (n = 8; age range, 82-93 years) were treated at a reduced dose. Restaging was performed after 3 and 6 cycles, followed by every 3 months for the first 2 years, and every 6 months thereafter. RESULTS: A total of 123 cycles were administered to the study patients, with the median number of 6 cycles per patient (range, 1-9 cycles). At a median follow-up of 24 months (range, 1.5-87+ months), 22 patients were alive without evidence of disease and 3 patients had died (1 patient death was treatment-related). Twenty-four patients who were considered evaluable achieved a complete remission, 21 patients after 3 cycles and the remaining 3 patients after 6 cycles of treatment. Side effects generally were manageable, with only one patient requiring premature discontinuation of treatment due to protracted thrombocytopenia after three courses of therapy, and tolerance was not different between the two age groups. No recurrences were observed at last follow-up. CONCLUSIONS: The authors believe that chemotherapy using the CHOP regimen is highly effective in the treatment of patients with localized primary high grade gastric lymphoma.

Adult↗

PubMed2000

Treatment of advanced, refractory breast cancer with alternating docetaxel and epirubicin/cyclophosphamide plus human granulocyte colony-stimulating factor.

PURPOSE: A phase II study was performed to investigate the efficacy and tolerance of alternating docetaxel and epirubicin/cyclophosphamide plus recombinant human granulocyte colony-stimulating factor (G-CSF) in patients with advanced breast cancer who failed previous non-anthracycline/taxane-containing palliative chemotherapy. PATIENTS AND METHODS: Between November 96 and June 98, a total of 45 patients participated in this trial. Chemotherapy consisted of docetaxel 100 mg/m2 given as a 1-h infusion on day 1, and epirubicin 100 mg/m2 plus cyclophosphamide 800 mg/m2 both administered on day 21. G-CSF 5 microg/kg/day was given subcutaneously from days 22-28 during each cycle. Treatment courses were repeated every 42 days for a total of three courses unless prior evidence of progressive disease. RESULTS: The overall response rate was 57.8% (95% confidence interval, 42.1-72.3%), including seven complete (15.5%) and 19 partial remissions (42.3%); nine patients (20%) had stabilization of disease and 10 (22.3%) progressed. The median time to treatment failure was 7.0 months (range 1.5-26.0), and the median overall survival time 15.0 months (range 2.0-37.0+) with 12 patients (27%) currently still alive with metastatic disease. Myelosuppression was commonly observed with WHO grade 3/4 neutropenia in 20 patients (44%) complicated by septicemia in five (11%). Severe nonhematologic toxicity included stomatitis in five patients (11%), skin and peripheral neurotoxicity each in one patient; alopecia was seen in all 45 patients with complete hair loss in 26 (58%). CONCLUSIONS: Our data suggest that alternating docetaxel and epirubicin/cyclo-phosphamide plus G-CSF is an effective and tolerable second-line combination regimen for the treatment of advanced breast cancer.

Adult↗

PubMed2000

Treatment of unresectable, locally advanced pancreatic adenocarcinoma with combined radiochemotherapy with 5-fluorouracil, leucovorin and cisplatin.

The aim of the study was to evaluate the effectiveness and safety of a combined treatment modality including systemic chemotherapy with 5-fluorouracil (FU), leucovorin, cisplatin and external beam radiotherapy in patients with locally advanced pancreatic cancer. Systemic chemotherapy consisted of FU 400 mg m(-2) and leucovorin 20 mg m(-2) both given as intravenous bolus injection on days 1-4, plus cisplatin 20 mg m(-2) administered as 90-min infusion on days 1-4. Treatment courses were repeated every 4 weeks x 6 unless prior evidence of progressive disease. Radiation therapy using megavolt irradiation of > or = 6 MV photons with a 3- or 4-field technique was delivered during the second and third chemotherapy course, that was reduced in dose by 25%. Between October 1994 and July 1996, a total of 38 patients were entered onto this trial, all of whom were assessable for toxicity and survival. Eighteen of these (47%) had objective remissions to combined radiochemotherapy, including four CR (11%), 13 (34%) had stable disease and seven patients (18%) showed tumour progression during treatment. The median progression-free interval of the entire study population was 10 months (range 3-32), and median overall survival was 14.0 months (range 3-45+ months); 53% of all patients were alive at 12 months, and 18% of patients were alive at 24 months respectively. Severe haematological side-effects comprised neutropenia in 18%, thrombocytopenia in 8% and anaemia in 11%. The most frequent non-haematological side-effects were nausea/vomiting (WHO grade 3: 18%), and diarrhoea (grade 3: 13%). This combined radiochemotherapy regimen was tolerable and effective in patients with locally advanced pancreatic cancer. Since therapeutic results, in fact, compare favourably with other series, including surgical treatment of potentially resectable tumours, further evaluation of combined treatment modalities in the neoadjuvant setting seems warranted.

Adenocarcinoma↗

PubMed2000

Phase II study of second-line oxaliplatin, irinotecan and mitomycin C in patients with advanced or metastatic colorectal cancer.

The aim of this phase II study was to investigate the therapeutic value of second-line treatment with oxaliplatin, irinotecan (CPT-11) and mitomycin C (MMC) in patients with metastatic colorectal cancer pretreated with 5-fluorouracil (5-FU)-based chemotherapy. A total of 10 patients with metastatic colorectal cancer, all of whom had developed progressive disease from advanced or metastatic colorectal cancer while receiving or within 6 months after discontinuing first-line chemotherapy with 5-FU and leucovorin, were entered in this study. At the time of relapse, cytotoxic chemotherapy consisting of oxaliplatin 80 mg/m2 plus CPT-11 80 mg/m2 given i.v. on therapeutic day 1, and MMC 6 mg/ m2 given i.v. on day 15, respectively, was initiated. Treatment courses were repeated every 4 weeks for a total of six courses unless there was prior evidence of progressive disease. The overall response rate was 30% with three partial responses for all 10 assessable patients. Two additional patients (20%) had stable disease and five patients (50%) progressed. The median overall survival duration has not been reached yet and is longer than 7.1 months (range 2-23.5+) from the beginning of second-line therapy. Four patients are currently alive with progressive disease. The tolerance of second-line treatment was generally mild to moderate and easy to treat. Our data suggest that the combination of oxaliplatin, CPT-11 and MMC in patients with metastatic colorectal cancer pretreated with 5-FU-based chemotherapy is feasible and has substantial antitumor activity. Further evaluation of this regimen seems warranted.

Adult↗

PubMed2000

Oxaliplatin-induced fever and release of IL-6.

BACKGROUND: Oxaliplatin is a novel cytotoxic agent with documented activity in colorectal cancer. Side effects are generally moderate, and include peripheral neuropathy along with mild bone marrow suppression and gastrointestinal side effects. To our knowledge, induction of febrile episodes by this agents has not been described in the literature. CASE REPORT: We present the case of a 74-year-old male patient admitted to our institution for palliative treatment of metastatic colorectal carcinoma. Due to progression during treatment with 5-fluorouracil and leucovorin, chemotherapy consisting of oxaliplatin 85 mg/m(2) on days 1 + 15 plus mitomycin C 8 mg/m(2) on day 1 repeated every 28 days was initiated. The first cycle of this combination was tolerated without side effects, but the patient experienced fever up to 39 degrees C starting 2 h after oxaliplatin administration on day 15 of the second cycle, which persisted for 3 days. Fever again recurred at the same interval following administration of oxaliplatin on day 1 of the next cycle. Blood samples taken at regular intervals disclosed an increase in IL-6 serum levels parallel to the body temperature curve, with the peak corresponding to the highest temperature, while C-reactive protein values remained unchanged. In spite of intensive premedication with steroids, antipyretics and clarithromycin, fever promptly recurred during the third cycle of treatment. CONCLUSION: Our data suggest a clear- cut correlation between fever, the release of IL-6 and oxaliplatin administration. Whether IL-6 release is directly triggered by the application of oxaliplatin or is a bystander phenomenon, however, remains unclear at the moment.

Adenocarcinoma↗

PubMed2000

Value of peptide receptor scintigraphy using (123)I-vasoactive intestinal peptide and (111)In-DTPA-D-Phe1-octreotide in 194 carcinoid patients: Vienna University Experience, 1993 to 1998.

PURPOSE: To report our experience with both (123)I-vasoactive intestinal peptide (VIP) and (111)In-DTPA-D-Phe(1)-octreotide for imaging to identify primary and metastatic tumor sites in carcinoid patients. PATIENTS AND METHODS: One hundred ninety-four patients with a verified or clinically suspected diagnosis of a carcinoid tumor were injected with (111)In-DTPA-D-Phe(1)-OCT for imaging purposes, while 133 patients underwent scanning with both (123)I-VIP and (111)In-DTPA-D-Phe(1)-OCT in random order. Imaging results were compared with computed tomography scans, results of conventional ultrasound, endosonography, and endoscopy, and results of surgical exploration in case of inconclusive conventional imaging. RESULTS: Primary or recurrent carcinoid tumors could be visualized with (111)In-DTPA-D-Phe(1)-OCT in 95 (91%) of 104 patients; metastatic sites were identified in 110 (95%) of 116 patients. In 11 (51%) of 21 patients with suggestive symptoms but without identified lesions by conventional imaging, focal tracer uptake located the carcinoid tumor. In addition, metastatic disease was demonstrated in three patients after resection. In a direct comparison in the 133 patients who underwent both imaging modalities, (111)In-DTPA-D-Phe(1)-OCT was found to be superior to (123)I-VIP, with 35 (93%) of 38 versus 32 (82%) of 38 scans being positive in primary or recurrent tumors, 58 (90%) of 65 versus 53 (82%) of 65 being positive in patients with metastatic sites, and seven (44%) of 16 versus four (25%) of 16 being positive in patients with symptoms but otherwise negative work-ups. Overall, additional lesions not seen on conventional imaging were imaged in 43 (41%) of 158 versus 25 (25%) of 103 scans with (111)In-DTPA-D-Phe(1)-OCT and (123)I-VIP, respectively. CONCLUSION: Both peptide tracers have a high sensitivity for localizing tumor sites in patients with ascertained or suspected carcinoid tumors, with (111)In-DTPA-D-Phe(1)-OCT scintigraphy being more sensitive than (123)I-VIP receptor scanning. Both, however, had a higher diagnostic yield than conventional imaging, as verified by surgical intervention or long-term follow-up. The combination of both peptide receptor scans does not seem to further enhance diagnostic information.

Adult↗

PubMed2000

Treatment of hepatocellular cancer with the long acting somatostatin analog lanreotide in vitro and in vivo.

Based on the fact that somatostatin (SST) analogs have given promising results for treatment of hepatocellular cancer, we performed both in vitro and in vivo investigations to define the role of a depot formulation of the long acting SST-analog lanreotide (LAN). A decrease of cells in the S-phase as compared to controls (p<0.03) followed by a significant, dose-dependent induction of apoptosis could be demonstrated in Hep G2 cells along with a dose-dependent influence of the peptide on cellular proliferation. Northern blotting demonstrated the presence of mRNA for SSTR subtypes 2, 3 and 4 in Hep G2 cells, but only slight SSTR expression in normal liver tissue. In addition, 21 untreated patients with advanced HCC not amenable to surgery were administered 30 mg of LAN by deep intramuscular injection every 14 days until documented disease progression. Fifteen of these patients also underwent scanning with commercially available 111In-DTPA-D-Phe1-Octreotide (111In-OCT) to define the in vivo expression of SSTR. No positive 111In-OCT scans were obtained, indicating the absence of relevant amounts of functional SSTR2 in HCC. One patient (5%) showed a partial response to treatment, 8 patients had stable disease (38%), while the remaining patients progressed during treatment. The median survival was 4.2 months (range 1.2-13+), and the median time to progression was 2.5 months (range, 1.5-7+). However, 4 patients (19%) had an increase in WHO performance status lasting between 2.5 and 6 months, 5 patients (24%) had an increase in body weight, while pain markedly improved in 1 additional patient (5%). In total, 5 patients (24%) had a decrease in serum-AFP levels by at least 30%. Our results clearly indicate the ability of LAN to decrease the S-phase fraction along with induction of apoptosis in Hep G2 cells in a dose-dependent manner. Our data suggest clinical potential of SST-analogs in HCC and indicate that suboptimal doses of the peptide might have been administered in our series.

Adolescent↗

PubMed1999

Treatment of advanced breast cancer with gemcitabine and vinorelbine plus human granulocyte colony-stimulating factor.

PURPOSE: A phase II trial was performed to investigate the efficacy and tolerance of gemcitabine, vinorelbine, and recombinant human granulocyte colony-stimulating factor (G-CSF) in advanced breast cancer. PATIENTS AND METHODS: Between April 96 and August 97, 60 patients entered this trial. Forty-five patients were previously untreated and 15 patients had failed previous palliative chemotherapy with (n = 10) or without anthracyclines (n = 5). Therapy consisted of gemcitabine 1000 mg/m2 on days 1 + 15 + 21 and vinorelbine 40 mg/m2 on days 1 + 21, both diluted in 250 ml saline and infused over 30 min. G-CSF was administered at 5 microg/kg/day subcutaneously from days 2-6 and 22-26. Courses were repeated every 5 weeks. Treatment was continued in case of response or stable disease until a total of six courses. RESULTS: The overall response rate was 55.5% for patients who had not received prior palliative chemotherapy (95% confidence interval, 40%-70.3%), including 5 CR (11.1%) and 20 PR (44.4%); 12 patients (27%) had stable disease (SD), and 8 (18%) progressed. Second-line treatment with this regimen resulted in 6/15 (40%) objective remissions, 5 had SD, and 4 PD. The median time to progression was 9.5 months (range, 1.5-28) in previously untreated patients, and 7.0 months (range, 2-23) in those who had failed prior chemotherapy. After a median follow-up time of 15 months, 44 patients (73%) are still alive with metastatic disease. Myelosuppression was commonly observed, though WHO 3 and 4 neutropenia occured in only 9 (15%) and 2 patients (3%), and was never complicated by septicaemia; grade 3 anemia was noted in 2 patients. Severe (WHO grade 3) nonhematologic toxicity was rarely observed, and included nausea/emesis in 3 and constipation in 2 patients. CONCLUSIONS: Our data suggest that gemcitabine and vinorelbine plus G-CSF is an effective and tolerable first- as well as second-line combination regimen for treatment of advanced breast cancer.

Adult↗

PubMed1999

Treatment of advanced pancreatic cancer with the long-acting somatostatin analogue lanreotide: in vitro and in vivo results.

Fourteen patients with metastatic pancreatic adenocarcinoma were treated with the long-acting somatostatin (SST) analogue lanreotide. No objective response was obtained, and the median survival was 4 months (range 1.8-7 months). Pancreatic cancer could not be visualized by means of SST-receptor (R) scintigraphy in our patients. In vitro data also demonstrated absence of SSTR2 expression, suggesting pancreatic cancer not to be a potential target for treatment with SST analogues.

Adenocarcinoma↗

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

Successful treatment of an advanced hepatocellular carcinoma with the long-acting somatostatin analog lanreotide.

Treatment options for hepatocellular cancer apart from surgical resection are limited because of the drug-refractory nature of this disease. Little is known about the role of somatostatin-receptors in hepatocellular cancer, and somatostatin analogs have not been investigated for treatment of this malignancy. We present the case of a 68-yr-old male, who was successfully treated with the long-acting somatostatin analog lanreotide.

Aged↗

PubMed1999

Vinorelbine and carboplatin in recurrent and/or metastatic squamous cell carcinoma of the head and neck.

A phase II trial was performed to assess the safety and efficacy of the semisynthetic vinca alkaloid vinorelbine (VNR) when combined with carboplatin in recurrent and/or metastatic squamous cell carcinoma of the head and neck. Treatment consisted of VNR 30 mg/m2 in 250 ml saline, infused over 30 min on days 1 + 8, and carboplatin 300 mg/m2 in 1,000 ml saline, infused over 2 h on day 1. Treatment was continued in patients achieving objective response or stable disease for a total of 6 courses. 24 patients entered this trial, 12 of whom had received prior induction chemotherapy and radiation, 2 had palliative chemotherapy and 10 had only radiation and/or surgery. We observed 2 partial response (9.5%), stable disease in 6 patients (28.5%) and progressive disease in 13 (62%). The dose-limiting toxicity was myelosuppression with grade 3 or 4 leukocytopenia in 11 patients (46%). Thrombocytopenia was seen in only 2 patients. The most frequent nonhematological toxicity was an acute pain at the tumor site. None of the patients experienced neurological symptoms or chemically induced phlebitis. VNR combined with carboplatin does not appear to improve the therapeutic armentarium in recurrent squamous cell carcinoma of the head and neck.

Adult↗

PubMed1999

Two consecutive phase II studies of 5-fluorouracil/leucovorin/mitomycin C and of gemcitabine in patients with advanced biliary cancer.

INTRODUCTION: Carcinoma of the biliary system is a rare tumor entity, and patients with advanced disease face a dismal prognosis. Because of the absence of standard chemotherapy for advanced biliary carcinoma, we have performed two consecutive studies to evaluate the clinical potential of 5-fluorouracil, leucovorin and mitomycin C as well as the novel antimetabolite gemcitabine in this disease. PATIENTS AND METHODS: A total of 39 consecutive patients suffering from locally inoperable or metastatic biliary cancer were enrolled in the study between March 1994 and October 1997. Twenty patients were treated with leucovorin 200 mg/m2 and 5-FU 400 mg/m2, both given as intravenous bolus on days 1-4, and mitomycin C 8 mg/m2 on day 1 (group A). Treatment cycles were repeated every 28 days. The second cohort included 19 patients, who received gemcitabine 1200 mg/m2 on days 1, 8 and 15 with a 2-week interval before the next treatment cycle (group B). Treatment was continued for a maximum of 6 cycles in the absence of progressive disease in both groups, and endpoints of the study were responses rates, survival and toxicity. RESULTS: In group A, 5 patients (25%) had a partial response (PR), 6 additional patients (30%) had stable disease (SD) and 9 patients (45%) progressed during treatment. The median survival was 9.5 months (range, 3-14.5) with the median time to progression being 4 months (range, 3-9). In group B, 3 patients achieved a PR (16%), 4 showed SD (21%), while the remaining 12 patients had progressive disease. A median survival of 6.5 months (range, 2-11.5) was obtained, and the median time to progression was 2.5 months (range, 1-6+). Toxicity was generally mild in both treatment arms, 6 patients in group A required dose reductions, while no dose adaptation had to be performed for gemcitabine. CONCLUSION: Our data suggest that treatment of advanced biliary cancer is feasible and can be safely performed with both regimens applied in our study. While administration of gemcitabine has resulted in only mild toxicities, its exact impact on the management of advanced biliary cancer should be evaluated in a controlled trial.

Adult↗