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1.
Br J Cancer ; 95(9): 1161-6, 2006 Nov 06.
Article in English | MEDLINE | ID: mdl-17031408

ABSTRACT

To evaluate the single agent activity, pharmacokinetics and tolerability of the novel tubulin targeted agent vinflunine (VFL) (320 mg m(-2) q 21 days) as second-line chemotherapy in patients with metastatic breast carcinoma (MBC). All patients had disease progression after anthracycline/taxane (A/T) therapy. They could have received a nonanthracycline adjuvant treatment and subsequently received a first-line A/T combination for advanced/metastatic disease; or relapsed >6 months after completion of adjuvant A/T therapy and were subsequently treated with the alternative agent; or relapsed within 6 months from an adjuvant A/T combination. Objective response was documented in 18 of 60 patients enrolled (RR: 30% (95% confidence interval (CI): 18.9-43.2%)). Among the responders, seven patients had relapsed during a period of <3 months from taxane-based regimen yielding a RR of 33.3%. The median duration of response was 4.8 months (95% CI: 4.2-7.2), median progression-free survival was 3.7 months (95% CI: 2.8-4.2) and median overall survival was 14.3 months (95% CI: 9.2-19.6). The most frequent adverse event was neutropenia (grade 3 in 28.3% and grade 4 in 36.7% of patients). No febrile neutropenia was observed. Fatigue (grade 3 in 16.7% of patients) and constipation (grade 3 in 11.7% of patients) were also common; these were non-cumulative and manageable permitting achievement of a good relative dose intensity of 93.5%. Vinflunine is an active agent with acceptable tolerance in the management of MBC patients previously treated with (A/T)-based regimens. These encouraging phase II results warrant further investigation of this novel agent in combination with other active agents in this setting or in earlier stages of disease.


Subject(s)
Breast Neoplasms/drug therapy , Vinblastine/analogs & derivatives , Adult , Aged , Anthracyclines/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Bridged-Ring Compounds/administration & dosage , Constipation/chemically induced , Disease Progression , Female , Humans , Leukopenia/chemically induced , Middle Aged , Nausea/chemically induced , Neutropenia/chemically induced , Survival Analysis , Taxoids/administration & dosage , Treatment Outcome , Vinblastine/pharmacokinetics , Vinblastine/therapeutic use
2.
Br J Cancer ; 94(10): 1395-401, 2006 May 22.
Article in English | MEDLINE | ID: mdl-16622447

ABSTRACT

A multicentre phase II trial to determine the efficacy of vinflunine as second-line therapy in patients with advanced transitional cell carcinoma (TCC) of the bladder; secondary objectives were to assess duration of response, progression-free survival (PFS) and overall survival (OS), and to evaluate the toxicity associated with this treatment. Patients had tumours that failed or progressed after first-line platinum-containing regimens for advanced or metastatic disease, or had progressive disease after platinum-containing chemotherapy given with adjuvant or neoadjuvant intent. Response and adverse events were assessed according to WHO criteria and NCI-CTC (version 2), respectively. Out of 51 patients treated with 320 mg m(-2) of vinflunine, nine patients responded to the therapy yielding an overall response rate of 18% (95% CI: 8.4-30.9%), and 67% (95%CI: 52.1-79.3%) achieved disease control (PR+SD). Of note, responses were seen in patients with relatively poor prognostic factors such as a short (<12 months) interval from prior platinum therapy (19%, including an 11% response rate in those progressing <3 months after platinum treatment), prior treatment for metastatic disease (24%), prior treatment with vinca alkaloids (14%) and visceral involvement (20%). The median duration of response was 9.1 months (95% CI: 4.2-15.0) and the median PFS was 3.0 months (95% CI: 2.4-3.8). The median OS was 6.6 months (95% CI: 4.8-7.6). The main haematological toxicity was grade 3-4 neutropenia, observed in 67% of patients (42% of cycles). Febrile neutropenia was observed in five patients (10%) and among them two were fatal. Constipation was frequently observed (but was manageable and noncumulative) and was grade 3-4 in only 8% of patients. The incidence of grade 3 nausea and vomiting was very low (4 and 6% of patients, respectively). Neither grade 3-4 sensory neuropathy nor severe venous irritation was observed. Moreover, and of importance in this particular study population, no grade 3-4 renal function impairment was observed. Vinflunine is an active agent for the treatment of platinum-pretreated bladder cancer, and these results warrant further investigation in phase III trials, either as monotherapy or in combination with other agents as treatment of advanced/metastatic TCC of the bladder.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Urinary Bladder Neoplasms/drug therapy , Vinblastine/analogs & derivatives , Adult , Aged , Aged, 80 and over , Carcinoma, Transitional Cell/secondary , Female , Humans , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Urinary Bladder Neoplasms/pathology , Vinblastine/therapeutic use
3.
Ann Oncol ; 14(4): 630-7, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12649112

ABSTRACT

BACKGROUND: Vinflunine is a novel vinca alkaloid obtained by semi-synthesis using super-acidic chemistry to selectively introduce two fluorine atoms at the 20' position of vinorelbine. In human tumour xenografts, vinflunine showed definite antitumour activity in seven out of 11 tumours tested compared with three out of 11 for vinorelbine. PATIENTS AND METHODS: In this phase I study, vinflunine was administered to 31 patients with advanced malignancies as a 10-min i.v. infusion every 3 weeks according to an escalating schedule of doses between 30 and 400 mg/m(2). RESULTS: Pharmacokinetic parameters and toxicities were assessed and, at 400 mg/m(2), three out of five patients experienced dose-limiting toxicity. At the maximum tolerated dose (MTD), i.e. 400 mg/m(2), the toxicity profile of vinflunine consisted mainly of mucositis, constipation and neutropenia of short duration. Vinflunine area under the curve increased as a proportion of the administered dose whereas no saturation of elimination was observed. CONCLUSION: The MTD of vinflunine was achieved at 400 mg/m(2) every 3 weeks. According to protocol rules, the recommended dose was established at 350 mg/m(2). A preliminary assessment of first patients included in early phase II trials led to reduction of the recommended dose to 320 mg/m(2) every 3 weeks for further development of vinflunine. Three partial responses (two in breast carcinoma, one in renal cell carcinoma) suggest that activity is likely to be seen in less heavily pretreated patient populations.


Subject(s)
Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacokinetics , Neoplasms/drug therapy , Vinblastine/analogs & derivatives , Vinblastine/adverse effects , Vinblastine/pharmacokinetics , Adult , Aged , Antineoplastic Agents/administration & dosage , Constipation/chemically induced , Drug Administration Schedule , Female , Humans , Infusions, Intravenous , Male , Maximum Tolerated Dose , Middle Aged , Mouth Mucosa/pathology , Neutropenia/chemically induced , Stomatitis/chemically induced , Vinblastine/administration & dosage
4.
Am J Clin Oncol ; 23(1): 60-4, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10683080

ABSTRACT

Weekly vinorelbine injection with cisplatin had been used in treatment of non-small-cell lung cancer. We performed a phase II trial to evaluate the efficacy and toxicity of a new schedule of vinorelbine and cisplatin in patients with previously untreated, inoperable (stage IIIB or stage IV) non-small-cell lung cancer. From April 1996 to May 1997, 52 patients were enrolled for study, and 50 patients were eligible and evaluable for both response and toxicity assessment. Therapy consisted of vinorelbine, 30 mg/m2, intravenously on days 1 and 5 of a 21-day cycle, and cisplatin 100 mg/m2 (reduced to 80 mg/m2 after the first seven patients) given on day 1. A total of 211 treatment courses were administered; the median number of cycles administered per patient was 4.5 (range: 1-6), the median dose intensity for vinorelbine was 16.9 mg/m2/week (84.4%), whereas that of cisplatin was 22.8 mg/m2/week (84.7%). Twenty-five patients responded to therapy for an overall response rate of 50%; one patient attained a complete response (2%). The main toxicities were vomiting, myelosuppression, and diarrhea, which included World Health Organization grade 3 or 4 nausea/vomiting (58% patients), anemia (41% patients), neutropenia (12% patients), and diarrhea (14%). The median duration of responses was 9 months. The median time to disease progression was 6.8 months (range 0.4-18.1 months). Median survival was 13 months, and 54% of patients were alive at 1 year. We conclude that this new schedule of vinorelbine and cisplatin achieves a high response with acceptable toxicity profile in patients with advanced non-small-cell lung cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Carcinoma, Non-Small-Cell Lung/secondary , Cisplatin/administration & dosage , Female , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Survival Analysis , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinorelbine
5.
Ann Oncol ; 10 Suppl 5: S41-5, 1999.
Article in English | MEDLINE | ID: mdl-10582138

ABSTRACT

Initial studies of vinorelbine (Navelbine) given as a single agent to patients with operable non-small-cell lung cancer (NSCLC) showed that overall response rates of the order of 30% could be obtained with a schedule of 30 mg/m2 given weekly. Although such high levels of response have seldom been obtained when vinorelbine is given alone in one arm of a comparative study, the level of activity is clearly worthwhile and represents a significant improvement over supportive care. Combination therapy with cisplatin has been highly successful, establishing Vinorelbine as a safe well-tolerated agent which provides considerable activity, and experience from large phase III studies suggests that the combination of vinorelbine and cisplatin could represent a reference schedule against which other therapy should be compared.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Vinblastine/analogs & derivatives , Carcinoma, Non-Small-Cell Lung/pathology , Cisplatin/administration & dosage , Humans , Lung Neoplasms/pathology , Treatment Outcome , Vinblastine/administration & dosage , Vinorelbine
6.
Ann Oncol ; 10 Suppl 5: S47-51, 1999.
Article in English | MEDLINE | ID: mdl-10582139

ABSTRACT

The investigation of the activity of vinorelbine in non-small-cell lung cancer (NSCLC) has continued beyond the initial studies which established its single agent activity and defined the combination of vinorelbine and cisplatin as one of the standard treatments for inoperable NSCLC. Alternative partners to cisplatin have been evaluated in combination therapy with vinorelbine with promising results emerging from combinations with carboplatin, ifosfamide, mitomycin C and gemcitabine. Three drug combinations such as vinorelbine, cisplatin and ifosfamide can clearly produce high response rates in patients with good performance status at the time of treatment. The ability of vinorelbine to contribute to disease reduction either alone or in combination with other cytotoxic drugs has made it possible to consider its use in neo-adjuvant therapy, while the synergistic action of vinorelbine with radiotherapy has encouraged the use of sequential or concomitant chemoradiotherapy producing high response rates after completion of both modalities. The possible role of post-operative adjuvant treatment with Vinorelbine either alone or in combination with cisplatin is being assessed in a prospective trial.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Vinblastine/analogs & derivatives , Chemotherapy, Adjuvant , Cisplatin/administration & dosage , Combined Modality Therapy , Humans , Vinblastine/administration & dosage , Vinorelbine
7.
Am J Clin Oncol ; 22(2): 196-8, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10199461

ABSTRACT

The efficacy of combination therapy with vinorelbine, cyclophosphamide, and 5-fluorouracil was assessed in women who had received no prior therapy for locally advanced or metastatic breast cancer. Sixty patients with metastatic breast cancer who had finished any adjuvant therapy at least 6 months previously and who had not received treatment for advanced disease were entered onto the study. The schedule consisted of vinorelbine (Navelbine, Pierre Fabre Medicament) 25 mg/m2 on days 1 and 8, cyclophosphamide 500 mg/m2 on day 1, and 5-fluorouracil 500 mg/m2 followed by folinic acid 200 mg/m2 on days 1 and 8. Treatment was repeated every 21 days up to a maximum of 8 cycles. Objective responses were observed in 27 of 60 patients (45%; CI95 32.4-57.6) including 4 complete responses (6.7%; CI95 0-13) and 23 partial responses (38.3%; CI95 22.5-54.1). The responses were achieved in both visceral and nonvisceral sites and at the same rate for patients with multiple sites of disease. Neutropenia was dose limiting, with 40% of patients affected at grade 3 or 4, while other hematologic and nonhematologic toxicity was very mild. This schedule achieves good levels of response without the use of an anthracycline, so it is suitable either for patients who have been extensively exposed to anthracyclines during adjuvant therapy or for those who have other contraindications to their use.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Adult , Breast Neoplasms/pathology , Cyclophosphamide/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Leucovorin/administration & dosage , Middle Aged , Neoplasm Metastasis , Survival Analysis , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinorelbine
8.
Cancer ; 85(5): 1091-7, 1999 Mar 01.
Article in English | MEDLINE | ID: mdl-10091793

ABSTRACT

BACKGROUND: A prospective, multicenter, randomized, Phase III trial comparing the efficacy of combination chemotherapy with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) with a combination of vinorelbine and doxorubicin (NA) in the treatment of patients with advanced breast carcinoma was undertaken. METHODS: One hundred and seventy-seven patients who previously were untreated for recurrent or metastatic breast carcinoma were entered into the study; 7 patients could not be assessed. The final analysis relates to 85 patients who were treated with FAC and 85 patients who were treated with NA, of whom 21 (25%) and 44 (52%), respectively, had received prior adjuvant chemotherapy. RESULTS: The overall response rates were similar for the two treatments and were unaffected by prior exposure to adjuvant therapy; overall response rate (ORR) for FAC was 74% (95% confidence interval [95% CI], 65-83%), and the ORR for NA was 75% (95% CI, 66-84%). The activity of NA in patients with liver involvement was greater than that of FAC in terms of survival. Overall survivals were similar, with a median of 17.3 months for patients receiving FAC and 17.8 months for patients receiving NA. Severe toxicity was uncommon with World Health Organization Grade 3-4 neutropenia affecting only 7% of patients in each arm of the study. NA was associated with a higher incidence of mild to moderate constipation, neurotoxicity, and phlebitis, whereas FAC produced a slight excess of mild cardiotoxicity. CONCLUSIONS: The efficacy of these two regimens is very similar, although NA may be more active in a subset of patients with visceral metastatic disease, particularly liver involvement. It is clear that, in a direct comparison with an established three-drug regimen, the newer two-drug combination of NA demonstrated equivalent activity with no significant excess of Grade 3-4 toxicity.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Adult , Aged , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/pathology , Cyclophosphamide/administration & dosage , Disease Progression , Disease-Free Survival , Doxorubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Prospective Studies , Survival Analysis , Treatment Outcome , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinorelbine
9.
J Clin Oncol ; 14(1): 164-70, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8558192

ABSTRACT

PURPOSE: To evaluate the response rate and toxic effects of vinorelbine (VNB) administered as a single agent in metastatic squamous cell esophageal carcinoma. PATIENTS AND METHODS: Forty-six eligible patients with measurable lesions were included and were stratified according to previous chemotherapy. Thirty patients without prior chemotherapy and 16 pretreated with cisplatin-based chemotherapy were assessable for toxicity and response. VNB was administered weekly as a 25-mg/m2 short intravenous (i.v.) infusion. RESULTS: Six of 30 patients (20%) without prior chemotherapy achieved a partial response (PR) (95% confidence interval [CI], 8% to 39%). The median duration of response was 21 weeks (range, 17 to 28). One of 16 patients (6%) with prior chemotherapy had a complete response (CR) of 31 weeks' duration (95% CI, 0% to 30%). The overall response rate (World Health Organization [WHO] criteria) was 15% (CR, 2%; PR 13%; 95% CI, 6% to 29%). The median dose-intensity (DI) was 20 mg/m2/wk. VNB was well tolerated and zero instances of WHO grade 4 nonhematologic toxicity occurred. At least one episode of grade 3 or 4 granulocytopenia was seen in 59% of patients. A grade 2 or 3 infection occurred in 16% of patients, but no toxic deaths occurred. Other side effects were rare, and peripheral neurotoxicity has been minor (26% grade 1). CONCLUSION: These data indicate that VNB is an active agent in metastatic esophageal squamous cell carcinoma. Given its excellent tolerance profile and low toxicity, further evaluation of VNB in combination therapy is warranted.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Esophageal Neoplasms/drug therapy , Vinblastine/analogs & derivatives , Abdominal Pain/chemically induced , Adult , Aged , Antineoplastic Agents, Phytogenic/adverse effects , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/secondary , Drug Administration Schedule , Esophageal Neoplasms/mortality , Female , Hematologic Diseases/chemically induced , Humans , Male , Middle Aged , Paresthesia/chemically induced , Reflex, Abnormal , Reflex, Stretch , Survival Rate , Treatment Outcome , Vinblastine/adverse effects , Vinblastine/therapeutic use , Vinorelbine
10.
Semin Oncol ; 22(2 Suppl 5): 22-8; discussion 28-9, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7740332

ABSTRACT

Phase II studies of vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France) have been conducted mainly at a dose of 30 mg/m2/wk, and this schedule has been used extensively in the treatment of advanced breast cancer. Vinorelbine used in a first-line setting as a single agent in 25 patients with previously untreated advanced metastatic breast cancer produced objective responses in 15 patients (60%) and complete responses (CR) in five (20%). A large multicenter study to assess the response rate by the main site of disease involvement included 145 assessable patients. The overall response rate was 41% (10 CRs and 50 partial responses: skin, 70%; lymph nodes, 67%; primary tumor, 56%; lungs, 33%; measurable bone, 27%; and liver, 23%). The median time to disease progression was 25 weeks and the median overall survival duration was 18 months. Neutropenia was the principal toxicity with grade 3/4 suppression noted; however, this was not accompanied by serious infection (incidence of grade 3/4 infection < 1%). Other grade 3/4 toxicity also was uncommon. Another phase II study included 50 patients assessable for toxicity and response. The overall response rate was 50% (2% CRs). In a salvage setting (second- and third-line treatment), 33 patients were treated with an overall response rate of 30% (two CRs). Rates of toxicity were no greater than in first-line patients. The most notable results for combination vinorelbine therapy were with a schedule of vinorelbine 25 mg/m2 on days 1 and 8 and doxorubicin 50 mg/m2 on day 1, with cycles repeated every 21 days. The overall response rate for the 89 evaluable patients was 74% (19 [21%] CRs; 47 [53%] partial responses). These data indicate that vinorelbine is a highly active agent with a favorable toxicity profile in the treatment of breast cancer.


Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Vinblastine/analogs & derivatives , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Clinical Trials, Phase I as Topic , Clinical Trials, Phase II as Topic , Female , Humans , Salvage Therapy , Vinblastine/therapeutic use , Vinorelbine
11.
J Clin Oncol ; 11(7): 1245-52, 1993 Jul.
Article in English | MEDLINE | ID: mdl-8315421

ABSTRACT

PURPOSE: This study investigated the therapeutic effects of single-agent intravenous (IV) weekly Navelbine (vinorelbine or 5'-nor-anhydro-vinblastine; Pierre Fabre Médicament, Boulogne, France), a semisynthetic vinca alkaloid, in women who had received no prior chemotherapy for locally advanced or metastatic breast cancer. PATIENTS AND METHODS: One hundred fifty-seven patients with assessable advanced or metastatic breast cancer who had received no prior chemotherapy were entered onto the study. They were stratified into five groups according to the main assessable tumor target: lung, liver, lymph nodes, skin, and others. One hundred forty-five patients were assessable for toxicity and response using World Health Organization (WHO) criteria; the 12 patients who were not evaluated were excluded because they were found not to meet the eligibility criteria. Navelbine was administered as a weekly 30-mg/m2 short IV infusion, and treatment was continued until disease progression. RESULTS: The overall response rate (WHO criteria) was 41% (complete response [CR], 7%; partial response [PR], 34%; 95% confidence interval [CI], 33% to 49%). In addition, 30% of the patients had stable disease. The response rate according to target was lymph nodes (28 of 42), 67%; liver (nine of 39), 23%; lung (10 of 30), 33%; skin (21 of 30), 70%; primary tumor (10 of 16), 56%; and bone (three of 10), 30%. The median time to treatment failure was 6 months and the median survival was 18 months. A total of 1,673 cycles were given to 145 eligible patients. At least one episode of WHO grade 3 or 4 granulocytopenia was seen in 72% of the patients. Nausea and/or vomiting, anemia, and/or thrombocytopenia were seen in less than 1% of cycles. Other side effects were rare, and additional toxicities were documented in the following proportions of patients: grade 2 to 3 alopecia, 8%; infectious episodes, 6%; and peripheral neuropathy, 3%. CONCLUSION: Our data confirm that Navelbine has major single-agent antitumor activity as front-line therapy in advanced breast cancer. Given its excellent tolerance profile and low toxicity, it should be considered for inclusion in first-line combination chemotherapy regimens.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Vinblastine/analogs & derivatives , Adenocarcinoma/secondary , Adult , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Breast Neoplasms/pathology , Drug Administration Schedule , Female , Humans , Infusions, Intravenous , Middle Aged , Vinblastine/administration & dosage , Vinblastine/adverse effects , Vinblastine/therapeutic use , Vinorelbine
12.
Lab Invest ; 64(2): 157-66, 1991 Feb.
Article in English | MEDLINE | ID: mdl-1997730

ABSTRACT

After partial hepatectomy, the liver is capable of complete regeneration, restoring normal hepatic size, architecture, and function. To study the role of the extracellular matrix in regeneration, the temporal and spatial sequence of deposition of several of its components, including collagen types I, III, and IV, laminin, and fibronectin, in rat liver, after an 80% hepatectomy, was characterized by light microscopy immunohistochemistry. A minimum of five animals were studied for each date. In agreement with previous reports, subsequent to 80% hepatectomy, there was a brisk mitosis of hepatocytes. The mitotic activity was maximal at 48 hours, primarily in the periportal and centrilobular zones, and resulted in the formation of hepatocyte clusters and widening of the hepatic plates. Of the extracellular matrix components studied, laminin was the one demonstrating the most dramatic changes. By 24 hours, laminin appeared in the hepatic sinusoids reaching a maximum staining intensity at 48 hours. Intracellular laminin was prominent in numerous non-parenchymal cells, with many having the morphology, location, and desmin content characteristic of Ito cells. Laminin staining decreased in the sinusoids at 4 days; however, some intracellular staining of Ito cells was present even at 8 days after hepatectomy. At the completion of regeneration, there was no evidence of any substantial change in the ratio: extracellular matrix/cell mass. The results indicate that: (a) hepatocytes can divide without prior removal of the subsinusoidal extracellular matrix; (b) during regeneration, hepatocyte division precedes sinusoidal formation; (c) during hepatic regeneration, and in spite of the presence of laminin in Ito cells, no basement membranes are formed; (d) the prominent expression of laminin and its proposed functions in morphogenesis suggest a critical role for this matrix component in the formation and reorganization of the regenerating liver.


Subject(s)
Collagen/analysis , Extracellular Matrix/physiology , Fibronectins/analysis , Laminin/analysis , Liver Regeneration , Animals , Extracellular Matrix/ultrastructure , Liver/ultrastructure , Models, Biological , Rats , Rats, Inbred Strains , Time Factors
13.
Onkologie ; 14(1): 35-9, 1991 Feb.
Article in English | MEDLINE | ID: mdl-1647510

ABSTRACT

17 patients with advanced low-risk breast carcinoma not previously pretreated by cytostatic agents were treated by Vinorelbine (VIN), 5'-Nor-anhydro-vinblastine, a new semisynthetic compound of the vinca alkaloid series. A dose of 130 mg per week was administered in a hard gelatine formulation for at least eight weeks. Out of 15 evaluable patients, no complete or partial remission was observed. However, there were 9 patients (60%) achieving no change and tumor stabilization, respectively, lasting for a median of 3.0 months. Main toxicities were leukopenia (17.7%, WHO grade 3-4), nausea and vomiting (17.7%, WHO grade 3-4), and acute diarrhea (70.6%, WHO grade 1-4). Thus, further trials with the oral medication used for this study are not recommended.


Subject(s)
Antineoplastic Agents , Breast Neoplasms/drug therapy , Vinblastine/analogs & derivatives , Aged , Aged, 80 and over , Breast Neoplasms/mortality , Capsules , Carcinoma/drug therapy , Carcinoma/mortality , Carcinoma, Intraductal, Noninfiltrating/drug therapy , Carcinoma, Intraductal, Noninfiltrating/mortality , Combined Modality Therapy , Drug Evaluation , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Metastasis , Neoplasms, Hormone-Dependent/drug therapy , Neoplasms, Hormone-Dependent/mortality , Survival Rate , Vinblastine/administration & dosage , Vinblastine/adverse effects , Vinorelbine
15.
Med Oncol Tumor Pharmacother ; 6(4): 267-9, 1989.
Article in English | MEDLINE | ID: mdl-2615530

ABSTRACT

Nineteen patients with advanced head and neck cancer were given mitozolomide (MTZ), i.v. infusion, every 6 weeks. The starting dose was 100 mg m-2. When it was well tolerated, dose escalation was performed up to 110-115 mg m-2. The limiting toxicity was thrombocytopenia, often mild, but occasionally severe, with hemorrhage and the need for platelet transfusions in two patients. The platelet nadir was 85 x 10(9) l-1 (11-225). No response was observed in 14 evaluable patients. MTZ, according to this schedule and dosage does not show significant activity in human squamous cell head and neck cancer.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Head and Neck Neoplasms/drug therapy , Nitrogen Mustard Compounds/therapeutic use , Adult , Aged , Antineoplastic Agents/adverse effects , Bone Marrow/drug effects , Drug Administration Schedule , Humans , Infusions, Intravenous , Male , Middle Aged , Neoplasm Recurrence, Local , Nitrogen Mustard Compounds/adverse effects , Thrombocytopenia/chemically induced
16.
Invest New Drugs ; 6(4): 323-5, 1988 Dec.
Article in English | MEDLINE | ID: mdl-3229944

ABSTRACT

Twenty-two patients with advanced colorectal cancer (CRC) (12 without prior chemotherapy) and fourteen with pretreated breast cancer (BC) were given mitozolomide (MTZ), IV infusion, every six weeks. The starting dose was 90 mg/m2. When it was well-tolerated, dose escalation was done up to 100-115 mg/m2. Toxicity was mild, limited to thrombocytopenia with a median nadir of 1.27 x 10(5) (0.20-4.86). No response was observed in these patients. MTZ, according to these schedule and dosage, does not show activity in human CRC and pretreated BC.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Colorectal Neoplasms/drug therapy , Nitrogen Mustard Compounds/therapeutic use , Adult , Antineoplastic Agents/adverse effects , Drug Evaluation , Female , Humans , Male , Middle Aged , Nitrogen Mustard Compounds/adverse effects
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