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Biomedical subjects

E Cvitkovic

Publications and source records attributed to E Cvitkovic.

At least 127 records · Page 7Linked to original sources
PubMed1991

Recurrent and/or metastatic head and neck squamous cell carcinoma: a clinical, univariate and multivariate analysis of response and survival with cisplatin-based chemotherapy.

One hundred two patients with recurrent and/or metastatic head and neck squamous cell cancer were entered into four consecutive phase II trials, all cisplatinum (C-DDP, 100 mg/m2/cycle)-based. The two combinations tried were C-DDP, bleomycin, and fluorouracil (CFB) on 54 patients, and cisplatinum and vindesin in 36 patients (CV). The CFB combination was given with C-DDP by continuous infusion over 96 hours (23 patients) or on day 1 (31 patients). The CV regimen was also given in two different schedules, with VDS at 3 mg/m2/g weekly (12 patients) or by a 96-hour continuous infusion (0.6 to 1.0 mg/m2/d) in 24 patients. The following variables: sex, age, performance status, previous therapy, local recurrence, length of disease-free interval (DFI), distant metastases, weight loss, primary site, histological differentiation, type of chemotherapy, previous chemotherapy, evaluable/measurable disease, erythrosedimentation rate, and their relation with response to chemotherapy (WHO) and survival were submitted to both univariate and multivariate analysis (Cox). Overall response rate (RR:CR + PR) was 25 (28%) of 90. In the CFB protocols, RR was 12 (22%) of 54 vs. 13 (38%) of 36 (P = 0.15, NS) in the CV combination group. For the four different combinations the RR was CFB C-DDPci 7 (30%) of 23, CFB C-DDP 1 hour 5 (16%) of 31, CV VDS weekly 2 (17%) of 12, CV VDSci 11 (45%) of 24. The patient populations were very different, with the latest combination consisting of metastatic patients exclusively. Univariate analysis of multiple variables showed age less than 60 years, PS:0 or 1, no previous therapy, absence of local relapse, metastatic disease, long DFI, and that measurable disease was significant for the probability of response. Median survival was 7 months for the 90 evaluated patients, 5 months for nonresponders, and 9 months for responders (P = 0.01). In the univariate analysis, significant factors for survival were PS:0 or 1, a weight loss below 10%, long DFI, response to chemotherapy, erythrosedimentation rate (ESR) of less than 30 mm/1st hr, presence of bone metastasis, and the number of metastases. Multivariate analysis shows PS, the absence of local relapse, and disease-free interval as significant prognostic factors for response. Multivariate analysis factors of significance for survival were PS, weight loss, and response to chemotherapy. The analysis of the clinical pattern showed an evolution in RR from 3 (8%) of 36 on previously irradiated local recurrent disease to 8 (73%) of 11 in previously untreated patients with metastatic disease at presentation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Nasopharyngeal carcinoma. Biology, natural history, and therapeutic implications.

Undifferentiated carcinoma of the nasopharyngeal type (UCNT) is a particular head and neck Epstein Barr virus (EBV)-related carcinoma. It has a specific geographic repartition and a short natural history. Radiotherapy allows a high rate of local control, but 80% of patients die with or of metastatic spread. This tumor is also very chemosensitive, but the role of chemotherapy is still controversial. The Gustave Roussy experience (1984-1989) in this field is described. An 80% response rate in metastatic disease, 10% of unmaintained long-term complete responders after chemotherapy, and the achievement of 66% complete response with bleomycin-epirubicin-cisplatin (BEC) regimen in locally advanced disease are the main arguments for a primary role for chemotherapy in this potentially curable disease.

Carcinoma↗
PubMed1990

Treatment of advanced squamous cell carcinoma of the skin with cisplatin, 5-fluorouracil, and bleomycin.

The authors treated 14 patients with advanced squamous cell carcinoma (SCC) of the skin or lip with one to four cycles of combination chemotherapy consisting of cisplatin by bolus injection, and 5-fluorouracil (5-FU) and bleomycin by continuous 5-day infusion. Objective responses were seen in 11 of the 13 evaluable patients (84%). Four patients had a complete remission (30%) and seven patients, a partial remission (54%). Local control after definitive complementary radiation and/or surgical treatment was achieved in seven patients. Toxic side effects was acceptable; they consisted of nausea and vomiting in all patients, transient skin changes, hematologic (Grade 3/4) abnormalities in four patients, and pulmonary fibrosis in one elderly patient. These results show that this chemotherapy combination could play a role in reducing the tumor mass and in facilitating definitive treatment to obtain better functional and cosmetic results in advanced SCC of the skin.

Adult↗
PubMed1990

A phase II study of cisplatin and continuous infusion of vindesine in metastatic head and neck squamous cell cancer.

The chemotherapeutic treatment of recurrent and/or metastatic squamous cell carcinoma (SCC) of the head and neck (H & N) has a very dismal prognosis, with survival usually not exceeding 1 year. Reported objective response rates vary between 3% and 70%. This difference appears largely attributable to the heterogeneity of the patient populations included in most published Phase II studies in H & N cancer. They usually include together initially metastatic, recurrent, and post primary treatment metastatic disease patients. These patients respond differently to chemotherapy. Because of this situation, we decided to study a more homogeneous patient population consisting of metastatic patients only. Cisplatin (CDDP) and vindesine (VDS) are active agents in H & N SCC. As VDS has a cycle-specific activity, the therapeutic index may be increased if it is administered in a continuous infusion (CI) schedule. Thirty-three patients with metastatic H & N (69% biopsy proven) were treated with a combination regimen including CDDP (100 mg/m2) day 1 and VDS 0.6 to 1 mg/m2 for 96 hours of CI. Thirty-one patients were evaluable for response: five had a complete response (CR; 16%) and 11 had a partial response (PR; 36%) with an overall rate response of 52% (95% confidence limit: 33% to 70%). Median duration of CR was 6.4 months (3 to 19 months) and 4.4 months for PR (3 to 6 months). A decrease in the leukocytes was the main toxicity encountered with this regimen. This combination regimen containing CDDP and CI VDS was well tolerated and active in H & N SCC. The incorporation of an active vinca-alkaloid in neoadjuvant regimens should be considered.

Adult↗
PubMed1990

High complete response in advanced nasopharyngeal carcinoma with bleomycin, epirubicin, and cisplatin before radiotherapy.

Undifferentiated carcinoma of nasopharyngeal type (UCNT) is a geographically endemic, Epstein-Barr virus-related carcinoma of epidermoid origin with reported 5-year survival rates of 15%-40% when treated with radiotherapy alone. Although UCNT can be well controlled locally by radiation therapy, in advanced nodal stage N3 [International Union Against Cancer-American Joint Committee on Cancer (UICC-AJCC, 1987)] the survival rate is below 20%, primarily because of metastatic spread in 80% of the fatalities. We report a pilot study of 41 patients with nonmetastatic, locoregionally advanced disease (85% of the patients had a nodal status greater than or equal to N2C-N3; 43% had T4 primaries), during which we used a combination of 100 mg of cisplatin/m2 on day 1, 15 mg of bleomycin by intravenous push and 12 mg/m2 by continuous infusion on days 1-5, and 70 mg of epirubicin/m2 on day 1 every 21 days for three cycles before definitive radiation therapy with 70 Gy for 7 weeks. Twenty-seven of 41 patients (66%; 95% confidence interval = 52.5%-80.5%) achieved a clinical complete response, and 40 of 41 (98%) had a major objective response after chemotherapy. Two deaths were treatment related, but side effects were moderate, and the overall treatment sequence was feasible. At the end of radiation therapy, all 39 assessable patients were in complete response, with a median follow-up of 21+ months (greater than 10-greater than 31); 33 (80%) patients had no evidence of disease. We believe that such a complete response rate in a high-volume disease with the use of combined modality treatment indicates a therapeutic gain in UCNT. Researchers performing a multicenter international controlled trial will test this hypothesis and compare local control, disease-free, and overall survival of the therapeutic sequence presented here with radiotherapy alone.

Adolescent↗
PubMed1990

Phase II study of cisplatin and continuous-infusion 5-fluorouracil and bleomycin for recurrent and metastatic head and neck squamous-cell carcinoma.

5-Fluorouracil (5-FU) and bleomycin (BLM) are active agents in head and neck squamous-cell cancer (H-N-scc). Less toxicity and an enhanced activity have been reported when these agents are administered by continuous infusion (CI), with or without a bolus of cisplatin (CDDP), another active agent. Thirty-three patients with recurrent and/or metastatic head and neck squamous cell carcinoma were treated with a combination regimen including CDDP (100 mg/m2) on day 1 plus BLM (15-mg bolus followed by 16 mg/m2/day by CI) and 5-FU (650 mg/m2/day by CI) on days 1-5 every 3 weeks. Thirty-one patients were evaluable for toxicity and response. The response rate (RR) was 15% (5 of 31), with one complete response (CR) and four partial responses (PRs), at a confidence interval of 95% (0-34%). Four of the five responders had not received previous radiotherapeutic treatment. Toxicity was deemed acceptable; nausea and vomiting and stomatitis were moderate. Only one patient had irreversible renal toxicity, after two cycles of chemotherapy. No symptomatic lung toxicity was observed. Good antitumour activity was noted for previously untreated disease (3 of 4; 75% RR). This combination of drugs proved to be inactive, however, in previously irradiated recurrent and/or metastatic H-N-scc (1 of 25; 4% RR). These results underscore the need to be extremely attentive to different patient populations when selecting therapeutic schedules and when analyzing reported results.

Adult↗
PubMed1989

Undifferentiated carcinoma of nasopharyngeal type of tonsil.

A review of 2262 squamous cell carcinomas of the tonsillar region seen at the Institut Gustave-Roussy, Villejuif, France, from 1970 to 1986 showed 1837 well- and poorly differentiated squamous cell carcinomas and 425 undifferentiated squamous cell carcinomas. Eighteen patients with undifferentiated squamous cell carcinomas presented histologic characteristics of undifferentiated carcinomas of nasopharyngeal type. Radiosensibility and radiocurability (complete sterilization with 70 Gy administered) was found in this group with an excellent long-term control of local disease (77% at 10 years actuarial). Epstein-Barr virus-related serologic tests were performed for seven patients. Four of them presented the serologic anti-Epstein-Barr virus titer patterns, generally associated with undifferentiated carcinomas of nasopharyngeal type (1280 to 5120 for viral capsid antigen/IgG and 40 to 320 for viral capsid antigen/IgA). These observations confirm that undifferentiated carcinomas of the nasopharyngeal type may arise outside the nasopharynx.

Adult↗
PubMed1989

Phase II study of mitozolomide (M & B 39,565) in head and neck cancer.

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.

Adult↗
PubMed1989

96-hour continuous infusion of cis-platinum, 5-fluorouracil and bleomycin in recurrent or metastatic head and neck squamous cell carcinoma, unexpected anemia.

Cis-platinum, 5-fluorouracil and bleomycin are active agents in head and neck SCC. When given by continuous infusion (C.I.) lower toxicity and increased activity have been reported. A 4-day trial of triple C.I. including these reagents was conducted for recurrent and/or metastatic head and neck SCC. Cis-platinum 25 mg/m2/day, 5-FU 650 mg/m2/day and bleomycin 10 mg/m2/day were given for 4 days every 4 weeks. Twenty-nine patients were entered, 27 were evaluable for toxicity and 3 for response. The response rate was 30% (one CR and seven PR). Patient compliance was poor (one central and one peripheral i.v. line) and toxicity was acceptable except for the unexpected anemia; 48% of patients required red cell transfusion. One patient died of bleomycin-induced lung toxicity and minor renal toxicity related to parenteral hydration was observed in the first 16 patients. In conclusion, this combination is moderately active in recurrent and/or metastatic head and neck SCC. Patient compliance was poor and cumulative anemia was an unexpected toxic event. Further trials with this triple C.I. chemotherapy are not recommended for the alcoholic, undernourished, very advanced cancer patient population.

Adult↗
PubMed1988

Early metastatic cancer of unknown primary origin at presentation. A clinical study of 302 consecutive autopsied patients.

We studied 302 consecutive autopsied patients who presented with carcinoma of unknown primary origin. The most frequent metastatic sites were the nodes, lung, and bone. The primary site was identified while patients were alive in 27% and at autopsy in 57%; the site remained unidentified in 16%. The pancreas (26.5%), lung (17.2%), kidney (4.6%), and colorectum (3.6%) were the most frequent primary sites, but the reliability of diagnostic tests used in the search for this site was disappointing. Survival was identical in patients whose primary site was discovered while alive, at autopsy, or remained unknown. The number of metastases at presentation was the major prognostic factor. Analysis of autopsy data demonstrated that patients with carcinoma of unknown primary origin pursue a different course than expected when the primary site is the first manifestation of the disease. On the basis of these results and the results of other modern series, we suggest an approach consisting of a limited initial workup but with greater emphasis on modern histochemistry studies and immunohistopathologic and other kinetic and morphologic parameters to understand the patient tumor characteristics better and base the clinical management on an individual basis.

Actuarial Analysis↗
PubMed1987

Bone marrow biopsies in patients with undifferentiated carcinoma of the nasopharyngeal type.

Bone marrow involvement was found in 21 of 56 patients with undifferentiated carcinoma of the nasopharyngeal type UCNT whose nasopharyngeal and bone marrow biopsies were available. Radiotherapy and chemotherapy (cisplatin, 5-fluorouracil and bleomycin) were given because of distant metastases. The microscopic aspects of bone invasion were investigated and were classified into three subtypes osteolytic, osteosclerotic and mixed type. The UCNT patients population was 10 years younger than that studied previously. Both the extent of the primary tumor (T) and cervical lymph node status (N) exerted an influence on the probability of metastases developing. Chemotherapy given to patients must be improved because UCNT with bone metastases is a disease with a poor prognosis.

Adolescent↗
PubMed1981

VAB-3 combination chemotherapy of metastatic testicular cancer.

The initial response and long-term follow-up of 74 evaluable patients who received combination chemotherapy for metastatic nonseminomatous testicular cancer are reported. Patients were treated with a protocol (VAB-3) including vinblastine, actinomycin-D, bleomycin, and cis-dichlorodiammine platinum (DDP). VAB-3 alone caused complete remission (CR) in 54% (40/74) and partial remission (PR) in 26% (1974). Five patients with less than CR to chemotherapy achieved CR following surgical excision of residual mature teratoma after starting VAB-3 protocol, resulting in an overall CR rate of 61% (45/74). With a minimum follow-up of 24+ months, and a median follow-up of 35+ months for those still living, 45% (33/74) of the patients are living free of evidence of disease, 4% (3/74) are living with disease, and 51% (38/74) are dead. Response to VAB-3 protocol was examined with respect to performance status, histology, prior therapy, extent of disease, tumor markers, and duration of disease from diagnosis. No one died because of toxicity of VAB-3, and life-threatening toxicity was uncommon. Long survival is significantly associated (P less than 0.001) with achievement of CR. The treatment goal for metastatic testicular cancer is cure. The achievement of CR, using aggressive combination chemotherapy and surgery, is essential in reaching this goal.

Adolescent↗