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E Cvitkovic

Publications and source records attributed to E Cvitkovic.

At least 91 records · Page 5Linked to original sources
PubMed1996

Characterisation and clinical management of CPT-11 (irinotecan)-induced adverse events: the European perspective.

CPT-11 (Campto, irinotecan) is a promising new agent in the treatment of advanced colorectal cancer. Its safety has been assessed in light of the results from recent European phase II studies. In a pivotal French study in which CPT-11 350 mg/m2 was administered once every 3 weeks, neutropenia and delayed diarrhoea were the major adverse events: transient neutropenia occurred in 80% of patients, and severe neutropenia and febrile neutropenia in 47 and 15%, respectively. Delayed diarrhoea occurred in 87% of patients, with 39% having severe (grade 3 or 4) diarrhoea and 16% requiring hospitalisation. None of these adverse events was cumulative. Results of a pilot study to elucidate the mechanism of CPT-11-induced delayed diarrhoea suggest that this toxicity has a secretory mechanism with an exudative component. Early appropriate management of delayed diarrhoea may improve the safety profile of CPT-11. Indeed, the safety profile of CPT-11 was clearly improved in a later (currently ongoing) pan-European study: incidences of severe (grade 3 or 4) delayed diarrhoea and febrile neutropenia (+/-infection) were reduced from 39% to 23% (grade 4: 8% to 2.5%) and from 12% to 6%, respectively. Such an improvement could be attributed to a better understanding of the mechanisms of diarrhoea, improved patient selection criteria, better education of patients and physicians about management of delayed diarrhoea and the use of broad spectrum antibiotics when diarrhoea persisted despite loperamide therapy.

Adolescent↗
PubMed1996

Prognostic value of clinicopathological parameters in head and neck squamous cell carcinoma: a prospective analysis.

The prognostic weight of histological and biological factors was compared with that of known clinical prognostic factors in a population of 108 consecutive previously untreated patients with head and neck squamous cell carcinoma. Parameters studied were: tumour vascularisation, mitotic index, histological differentiation, nuclear grade, keratinisation, desmoplasia, growth pattern, inflammation, tumour emboli in peripheral vessels, keratins 6, 13, 19 immunohistochemical expression, cytofluorometric ploidy and S-phase. In multivariate analysis (Cox), only age and nodal status had a significant impact on the overall survival, whereas T stage was the only significant factor associated with locoregional failure. The cumulative incidence of metastases was correlated not only with age, T and N stage, but also with histological differentiation. All the other histological and biological factors studied failed to provide further prognostic information. These findings may help to select patients with high metastatic risk.

Age Factors↗
PubMed1996

Single agent activity of oxaliplatin in heavily pretreated advanced epithelial ovarian cancer.

BACKGROUND: Platinum-containing chemotherapy combinations achieve high response rates in women with advanced ovarian cancer. Unfortunately, most patients need further therapeutic options. Oxaliplatin (L-OHP) is a diaminocyclohexane (DACH) platinum analog active against human and murine cells in vitro and in vivo, including ovarian cells lines, with non-cross resistance characteristics with first (CDDP) and second (CBDCA) generation platinum compounds. The single agent activity of oxaliplatin in 34 consecutive platinum-pretreated ovarian cancer patients, not eligible for other phase II trials, was explored in a compassionate use program framework in a single institution. MATERIALS AND METHODS: Thirty-five patients (34 of them eligible) were treated by L-OHP at the median initial dose of 100 mg/sqm q 3 weeks (5 patients: 58-89 mg/m2; 24 patients: 90-100 mg/m2; 6 patients: 120-130 mg/m2) by short (30'-2 hours) i.v. infusion; the treatment was repeated every three weeks until treatment limiting toxicity or disease progression. RESULTS: Thirty-one patients (median previous chemotherapy lines: 3) were evaluable for antitumoral activity, with a 29% objective response rate. According to Markman's criteria, objective partial responses were seen in six out of 13 evaluable potentially platinum-sensitive patients (46%) and three responses in the 18 evaluable platinum-resistant patients (17%). The tolerance was excellent, with no grade 3-4 (WHO) leukoneutropenia despite previous ABMT and abdominopelvic radiotherapy in six and eight cases, respectively. There was no renal or ototoxicity, and nausea/vomiting were moderate. The only grade 3 (WHO) peripheral neuropathy recorded concerned a patient with a neurotoxicity status grade 2 at baseline. CONCLUSION: The 29% ORR single agent activity of oxaliplatin at hematological subtoxic doses in heavily pretreated ovarian cancer patients, with objective responses in platinum refractory patients, supports experimental data on non cross-resistance and a differential clinical toxicity profile to other available platinum compounds. The 12 month median overall survival of this poor prognosis patients cohort (62% platinum-refractory patients, median number of three previous chemotherapy lines) gives a strong empirical basis for the further exploration of oxaliplatin's role in confirmatory phase II and combination chemotherapy studies.

Adult↗
PubMed1996

Phase I-II trial of recombinant interferon alpha-2b with cisplatin and 5-fluorouracil in recurrent and/or metastatic carcinoma of head and neck.

The aims of this study were to establish the feasibility and toxicity of the biochemical modulation of the cisplatin (CDDP)-5FU combination by interferon alpha-2b (INF), and to assess its therapeutic efficacy in recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). The mandatory eligibility criteria included histologically proven SCCHN; a performance status <2; adequate bone marrow, hepatic, renal, and cardiac functions; and measurable and/or evaluable disease. The protocol was CDDP, 100 mg/m2 i.v. day 1; 5-FU, 1,000 mg/m2 in a c.i.v. infusion over 96 h; and INF 3.10(6) U/day s.c., begun 2 h before cisplatinum for 5 consecutive days, repeated every 3 weeks. Twenty patients were included and received 76 cycles (median number cycles/patient = three). Eighteen patients were evaluable for activity with an overall response rate (RR) of 30% [2 complete responses (CR) + 4 partial responses (PR)], which was 55% (5/9) in previously untreated and 9% (1/11) in previously treated patients. Myelosuppression (50%), mucositis (40%), loss of electrolytes (15%), and asthenia (20%) were the most frequent severe toxic effects. Notwithstanding, the protocol was feasible and well tolerated in this overall population with a poor prognosis. Median duration of response was 8 months, and median survival for the overall population was 8.5 months. This schedule is the test arm of an ongoing international multicentric phase III trial versus standard CDDP-5FU in the same SCCHN population.

Adult↗
PubMed1996

Neoadjuvant chemotherapy with cisplatin-vindesine-5-fluorouracil and folinic acid for locally advanced head and neck carcinoma.

The aim of this study was to establish the feasibility, evaluate the response rate, and assess the impact on local control and survival in locally advanced (bulky nodal) squamous cell carcinoma of the head and neck (SCCHN) patients treated with neoadjuvant chemotherapy consisting of cisplatin followed by continuous infusion of vindesine and fluorouracil with intermittent i.v. folinic acid. Eligibility criteria included histologically proven SCCHN, previously untreated locally advanced stage III-IV with measurable or evaluable disease, no distant metastases, an Eastern Cooperative Oncology Group (ECOG) performance status of less than 2, patient age of at least 18 years, and adequate bone marrow, hepatic, and renal functions. The protocol consisted of three cycles (day 1, day 21, day 42) of Cisplatin (CDDP) 100 mg/m2/day i.v. on day 1 immediately followed by 4 days (96 h) of continuous infusion of vindesine 0.8 mg/m2/day and 5-fluorouracil (5-FU) 600-700 mg/m2/day with folinic acid 150 mg/m2 i.v. every 6 h x 16 doses before locoregional treatment with radiotherapy preceded by radical surgery when appropriate. Twenty-nine patients were enrolled in this study, and 28 were evaluable for activity; an objective response rate of 55% (four complete responses, 12 partial responses) was achieved. Leukopenia and mucositis were the most frequent and severe toxicities. The addition of vindesine did not improve the activity of the CDDP-FU-folinic acid combination, but this may be partly because of the particularly poor prognosis of the present patient population, with 75% of stage IV bulky nodal disease (N2c-N3).

Adult↗
PubMed1996

Combined systemic chemoimmunotherapy in advanced diffuse malignant mesothelioma. Report of a phase I-II study of weekly cisplatin/interferon alfa-2a.

PURPOSE: To assess the tolerance, toxicity, and antitumoral activity of the weekly combination of cisplatin (CDDP) and interferon alfa-2a (IFNalpha2a) in advanced diffuse malignant mesothelioma (DMM). PATIENTS AND METHODS: Twenty-six patients with DMM (23 pleural and three peritoneal), previously untreated, were enrolled onto this study between August 1991 and December 1992. All patients had measurable disease defined by computed tomographic (CT) scan and diagnostic confirmation by histopathology review panel. IFNalpha2a (3 x 10(6) IU subcutaneously on days 1 to 4) and CDDP (60 mg/m2/wk on day 2) were given weekly. Initially planned as a 5-weeks-on/3-weeks-off treatment cycle, poor patient tolerance observed in the first 12 patients treated (group A) led to schedule adaptation with a shorter treatment sequence and prolongation of the rest period (4 weeks on/4 weeks off) in the following 14 patients (group B). At least two cycles were administered to each patient in the absence of tumor progression. RESULTS: Twenty-six patients were assessable for toxicity and 25 for efficacy (World Health Organization [WHO] criteria). Sixty-eight cycles of IFN/CDDP were given, with a median of three cycles per patient (range, one to five). Toxicity was mainly clinical, with progressive anorexia, asthenia, and prolonged nausea/emesis; these side effects have limited treatment acceptance in many patients. Thrombocytopenia and leukopenia were rarely noted as treatment-limiting toxicities. Objective responses (all partial) were obtained in 10 patients (95% confidence interval [CI], 20% to 60%). The median response duration was 11 months (range, 6 to 18). The median time to progression (TTP) for the whole cohort was 6 months and the median survival time was 12 months (range, 5 to 32). Objective responders had a significantly longer median TTP (21 months) and survival time (25 months) than nonresponders (3 and 8 months, respectively). CONCLUSION: The results of this pilot phase I-II study show encouraging antitumor activity in this traditionally resistant tumor, even if the specific contribution of IFN remains speculative and needs further clinical research. Our ongoing program is exploring the dose-intensity impact of IFN dose within the same combination.

Adult↗
PubMed1996

Intensive concomitant chemoradiotherapy in locally advanced unresectable squamous cell carcinoma of the head and neck: a phase II study of radiotherapy with cisplatin and 7-week continuous infusional fluorouracil.

PURPOSE: To evaluate an intensive concomitant chemoradiotherapy protocol of conventional radiotherapy with intermittent cisplatin (CDDP) and continuous-infusion fluorouracil (5-FU) in unresectable, locally advanced squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Fifty-seven patients with unresectable stage IV MO disease (International Union Against Cancer [UICC]/American Joint Committee on Cancer [AJCC], 1987) received radiotherapy 70 Gy followed by CDDP 80 mg/m2 and 5-FU 300 mg/m2/d. Response was assessed 2 months after treatment completion. RESULTS: Thirty patients (52%) received the full treatment schedule; 53 (93%) received full-dose radiotherapy, while 48 (84%) were given at least 75% of the planned chemotherapy doses. Severe mucositis (World Health Organization [WHO]) grade 3 to 4 was the limiting toxicity and was seen in 79% of patients. The median time for mucositis resolution was 8 weeks. Other toxicities were generally manageable, but there were four treatment related deaths (7%). Fifty patients were assessable for activity, with an overall response rate of 70% (95% confidence interval [CI], 58% to 82%). Complete response (CR) and partial response (PR) rates were 42% and 28%, respectively. CONCLUSION: This simultaneous combined-modality regimen was feasible at the cost of severe mucosal toxicity, which required hospitalization with nutritional, parenteral, and hydroelectrolytic support. The high response rate achieved (70%) did not translate into improved survival, probably due to patient eligibility. The likelihood of cure of this high-tumoral-volume patient population remains low (approximately 10%), despite the association of two therapeutic modalities at full standard therapeutic intensity.

Adult↗
PubMed1995

Undifferentiated nasopharyngeal cancer (UCNT): current diagnostic and therapeutic aspects.

Undifferentiated carcinoma of the nasopharynx (UCNT) is a particular head and neck epidermoid lineage tumor related to the Epstein Barr Virus (EBV). It has geographically selective endemic epidemiologic features, without relation to external carcinogens. Its systemic agressiveness is the source of most disease-related demises, because radiotherapy achieves excellent local control and a significant percentage of cure in patients with exclusive locoregional disease. Difference in the staying systems currently in use, the recent changes in imaging and radiotherapy technology, and the lack of distinction between UCNT and squamous cell carcinoma (SCC) of the nasopharynx in Western literature reports make for some difficulty in therapeutic results evaluation when analyzing available literature. Its chemosensitivity is a relatively recent acknowledged fact, and its use in metastatic patients results in a high percentage of objective responses, many of long duration. Neoadjuvant cisplatin-based chemotherapy seems to be of benefit, but outstanding controversies in this regard will be soon answered through ongoing phase III trials. After a review of the current literature of all the above-mentioned aspects of this fascinating nosologic entity, our own experience, both in metastatic and locoregional disease patients is analyzed.

Adolescent↗
PubMed1995

Tumor vascularization, mitotic index, histopathologic grade, and DNA ploidy in the assessment of 114 head and neck squamous cell carcinomas.

BACKGROUND: Quantification of tumor vascularization recently has been shown to a parameter of potential clinical significance. Several basic and clinical studies have demonstrated that tumor growth correlates significantly with angiogenesis. METHODS: To determine the utility of quantification of tumor vascularization and mitotic index for the pathobiologic assessment of head and neck squamous cell carcinoma, a prospective study of 114 consecutively recruited primary neoplasms was performed. Tumors were also studied for differentiation, keratinization, nuclear atypia, growth pattern, inflammation, desmoplasia, vascular tumor emboli, and DNA content. RESULTS: In this cohort, tumor vascularization was correlated with mitotic index (P < 0.001), nuclear grade (P = 0.03), presence of tumor emboli in the peripheral microvessels (P = 0.05), and lymph nodal status (P = 0.03). A strong relationship between poor differentiation and high N classification (P < 0.001), differentiation and keratinization (P < 0.001) and tumor cell emboli and clinically involved lymph nodes (P = 0.01) was also observed. Emboli were more rare in laryngeal and oropharynx/oral cavity tumors than in hypopharynx/epilarynx (P = 0.02). CONCLUSIONS: This study indicates that tumor vascularization, differentiation, and tumor emboli in peripheral microvessel network are important histologic parameters in the assessment of squamous cell carcinoma of the head and neck.

Adult↗
PubMed1995

Biology and treatment of nasopharyngeal cancer.

Nasopharyngeal carcinoma encompasses all epithelial tumors of epidermoid lineage that arise in this anatomic site. Two different histoclinical entities, squamous cell carcinoma (World Health Organization type 1) and undifferentiated carcinoma of the nasopharyngeal type (undifferentiated carcinoma of the nasopharyngeal type; World Health Organization types 2 to 3), share the primary site origin; the latter is more prevalent worldwide. Undifferentiated carcinoma of the nasopharyngeal type is a specific entity related to the Epstein-Barr virus with a particular geographic distribution among well-defined ethnic populations. Recent advances in the identification of the Epstein-Barr Virus genome, serologic markers, and environmental factors add to the knowledge and diagnosis of this disease. Improvements in irradiation techniques and modern imaging have increased local control, but distant failures remain the major problem in patients with locoregionally bulky disease, which is the most common form at presentation. The need for a staging consensus is being led by several new proposals incorporating computed tomography imaging. Neoadjuvant or simultaneous cisplatin-based chemotherapy combined with radiotherapy results in high local control rates and a high disease-free survival rate in several phase II trials. Ongoing controlled trials will soon establish a role for this multimodality approach. Metastatic or recurrent disease shows a high percentage of objective response rates and a substantial proportion of durable complete responses. This review focuses on recent advances in undifferentiated carcinoma of the nasopharyngeal type biology and management.

Adolescent↗
PubMed1994

[Undifferentiated carcinoma of the nasopharynx: epidemiological, clinical and therapeutic aspects].

Undifferentiated carcinoma of the nasopharynx (UCNT) is a particular head and neck epidermoïd lineage tumor related to the Epstein-Barr Virus (EBV). It has geographically selective endemic epidemiologic features, without relation to external carcinogens. Its systemic agressiveness is the source of most disease related demises, since radiotherapy achieves excellent local control and a significant percentage of cure in patients with exclusive locoregional disease. Differences in the staging systems currently in use, the recent changes in imaging and radiotherapy technology, and the lack of distinction between UCNT and SCC of the nasopharynx in Western literature reports make for some difficulty in therapeutic results evaluation when analyzing available literature. Its chemosensitivity is a relatively recent acknowledged fact, and its use in metastatic patients results in a high percentage of objective responses, many of long duration. Neoadjuvant cisplatin based chemotherapy seems to be of benefit, but outstanding controversies in this regard will be soon answered through ongoing phase III trials. After a review of the current literature of all the above mentioned aspects of this fascinating nosologic entity, our own experience in over 250 patients seen during the past 8 years, both in metastatic and locoregional disease patients is analyzed.

Adolescent↗