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E Cvitkovic

Publications and source records attributed to E Cvitkovic.

160 records · Page 9Linked to original sources
PubMed1977

Improvement of cis-dichlorodiammineplatinum (NSC 119875): therapeutic index in an animal model.

Cis-Dichlorodiammineplatinum (CPDD) NSC 119875 was given at toxic doses (3 mg/kg) to three groups of dogs. The renal toxicity was avoided with massive prehydration and with mannitol induced diuresis. The bone marrow toxicity was unaltered by either manipulation. The data presented indicate that a better therapeutic index has been achieved by osmotic diuresis with mannitol. Blood levels and urine levels measurements show that the pharmacokinetics of the drug are unaltered, the urinary concentration of drug being low in the first few hours, but with similar urinary drug recovery in all three groups.

Animals↗
PubMed1977

The renal pathology in clinical trials of cis-platinum (II) diamminedichloride.

The pathologic changes induced by Cis-platinum (II) diamminedichloride (CPDD) therapy in the kidneys are described in 12 patients with solid tumors and malignant lymphomas. According to dosage of CPDD the patients were divided into two groups: 1) low-dose group--.0.5-2 mg/kg daily, for 1 to 6 days; and 2) high-dose group--single injection of 3 or more mg/kg with concommitant mannitol-induced diuresis. Pathologic changes in the kidneys were essentially similar in both groups and consisted of focal acute tubular necrosis, affecting primarily the distal convoluted tubules and collecting ducts, dilatation of convoluted tubules, and formation of casts. These changes persisted as long as 29 days post CPDD therapy. In addition, the collecting ducts exhibited significant epithelial atypia. BUN and serum creatinine levels were elevated in both groups. The mean BUN/serum creatinine values were 54/2.2 mg/100 ml and 32/2.0 mg/100 ml for low and high-dose groups, respectively. Since the nephrotoxicity of CPDD is known to be dose-related, our findings suggest that mannitol-induced diuresis has considerably decreased the renal toxic damage of CPDD therapy in these patients.

Acute Kidney Injury↗
PubMed1977

High dose cis-platinum diammine dichloride: amelioration of renal toxicity by mannitol diuresis.

A clinical trial was undertaken to improve the therapeutic index of cis-platinum diammine dichloride with a concomitantly administered mannitol induced diuresis. Sixty patients, heavily pretreated, were entered; fifty-one are evaluable. The technique of concomitant osmotic diuresis and CPDD administration is described in detail. Doses ranged from 3 mg/kg to 5 mg/kg. At 5 mg/kg, dose-limiting renal, marrow and ototoxicity were seen, and resulted in one drug death. Marrow toxicity was moderate. Renal toxicity was limited to transient elevations in serum creatinine levels, except in some patients who had renal impairment prior to CPDD treatment. These patients had moderate renal toxicity. Serial treatments as frequently as once every 3 weeks were used to maintain responses. Serial high dose CPDD produced only mild renal dysfunction. Ototoxicity, usually subclinical, was quantitated audiometrically, and found to be dose related, but not clinically prohibitive at 4 mg/kg or less. The overall response rate (PR/MR) was 42%. Clinically significant responses in epidermoid carcinoma of the head and neck, adenocarcinoma of the ovary, and germ cell tumors of the testis were seen. All six responding patients with germ cell tumor of the testis, had been resistant to low dose (1mg/kg) CPDD. Two responding patients with ovarian adenocarcinoma had been resistant to alkylating agents.

Adenocarcinoma↗
PubMed1977

Clinical pharmacologic and therapeutic studies of bleomycin given by continuous infusion.

The clinical toxicology, clinical pharmacology, and therapeutic effects of bleomycin given by continuous intravenous infusion were studied in patients with far-advanced unresectable cancer. The toxicity of bleomycin given by that schedule was qualitatively and quantitatively the same as when it was given by daily intravenous "push"; mucocutaneous toxicity occurred regularly after 7-11 days of infusion. Careful monitoring of pulmonary function revealed minor changes in Total Lung Capacity and Pulmonary Diffusion Capacity in nearly all patients; however, overt pulmonary toxicity occurred in only six patients (5%). 111Indium-labeled bleomycin was used to follow blood levels of bleomycin; it correlated well with the levels determined by microbiologic assay and could be measured at levels lower than could be determined by bioassay. Useful therapeutic responses were seen in a variety of tumors; 30% patients with very far-advanced carcinoma of the cervix demonstrated CR or PR, an incidence higher than has been seen with other regimens. Sixty-nine percent of patients with disseminated germ cell neoplasms of the testis, refractory to bleomycin given by conventional dose schedules, have attained partial remission through the continuous infusion of bleomycin.

Bleomycin↗
PubMed1977

The evolution of mature teratoma from malignant testicular tumors.

During the period of 1969--1976, twelve cases of malignant germ cell tumor of the testis were seen in which the diagnosis was associated with the subsequent development of one or more metastases composed histologically of fully mature teratoma. These patients had a variety of primary germ cell tumors in the testis and were treated with radiation therapy and/or chemotherapy in addition to surgery, prior to the development of mature teratomas in different anatomic sites. The development of mature teratoma in this clinical setting seems to be a favorable prognostic sign, inasmuch as only one of the 12 patients has died with known persistent cancer. Since the incidence of this phenomenon seems to be increasing, the mechanism is probably related, directly or indirectly, to therapy.

Adolescent↗
PubMed1977

"Disappearing" spinal cord compression: oncolytic effect of glucocorticoids (and other chemotherapeutic agents) on epidural metastases.

Four patients suffering spinal cord compression resulting from epidural metastases were treated with adrenocorticosteroid hormones. For 2 patients, prompt relief of symptoms followed glucocorticoid therapy alone and was associated with marked shrinkage or disappearance of the metastasis, a direct oncolytic effect of the steroids. For the other 2 patients, glucocorticoids combined with other chemotherapeutic agents caused disappearance of the extradural tumor. For 1 patient, failure to recognize the oncolytic effects of the chemotherapy led to an unnecessary surgical procedure, and for a second patient an unnecessary operation was narrowly averted. Thus, for certain patients, glucocorticoids may occasionally have a marked oncolytic effect on epidural metastatic tumors.

Adolescent↗
PubMed1975

Studies on the sensitivity of anticancer agents of normal human cells in culture.

Two biopsies of human periosteal tissue have been tested for sensitivity to several antitumoral agents. The tests were performed during the lifespan of the cultured cells in order to reveal possible variations in sensitivity. The results indicate that the age of the donor affects drug sensitivity; cells obtained from the young donor show a higher growth potential, together with a variable sensitivity and morphology during their life in vitro, while cells from the adult donor have a lower growth potential, a constant sensitivity to chemotherapy and a constant morphology.

Adult↗
PubMedDate not supplied

Simultaneous chemoradiotherapy as salvage treatment in locoregional recurrences of squamous head and neck cancer.

This study was designed to determine if long-term palliation could be obtained in pre-irradiated locoregional recurrent squamous head and neck cancer patients, with the administration of simultaneous chemoradiotherapy. Mandatory eligibility criteria were histologically documented squamous head and neck cancer in previously irradiated territory, surgical or brachytherapy salvage unfeasibility, or patient refusal. The protocol consisted of radiotherapy, at a rate of 5 daily fractions of 2 Gy on alternate weeks, with simultaneous continuous intravenous infusion of 5-fluorouracil (5FU) at 800 mg/m2 and oral hydroxyurea (HU) at 1,000-1,500 mg/day for 5 days. Tolerance was good. Acute toxicity was low with no grade > or = III WHO hematologic toxicity observed. Nine patients had grade III mucositis, one had grade IV, three had grade III skin toxicity, and only four patients required a 20% to 30% 5FU dose reduction because of it. Two patients had hand and foot syndrome, and two had asymptomatic 5FU-related cardiac signs (1 ECG, 1 echographic+ECG). Chronic radiotherapy-related effects consisted of Hermitte's sign observed in two patients. Of 34 registered patients, 33 were evaluable for response. An overall rate of 55% (18 patients) of objective responses [complete response (CR) + partial response (PR)] was obtained, with 12 patients (36%) achieving local control of disease. The median survival was 11 months. These data show that palliation could be obtained for the majority of responding patients, and also suggest an improvement in the immediate prognosis with this type of salvage procedure for a selected group of recurrent squamous head and neck cancer patients.

Adult↗
PubMedDate not supplied

Phase II trial of recombinant interferon gamma in refractory undifferentiated carcinoma of the nasopharynx.

The presence of Epstein-Barr virus (EBV) genomes in the DNA of tumor cells of undifferentiated carcinoma of nasopharyngeal type (UCNT), associated with significant lymphocytic infiltration of tumor led to therapeutic trials with interferon (IFN) because of its antiviral, antiproliferative, and immunomodulatory properties. Fourteen patients with histologically proven UCNT (2 had locoregional disease alone and 12 metastatic disease) who were refractory to conventional chemotherapy, were treated with IFN gamma 20 x 10(6) U twice a week. Treatment was well tolerated. No objective response were achieved in the 13 evaluated patients, and all patients progressed after a median treatment duration of 10 weeks (6-32). IFN gamma seems unable to induce antitumor activity alone in such heavily pretreated patients. Its possible place in the management of UCNT is probably earlier in the natural history of this disease.

Adolescent↗
PubMedDate not supplied

Correlation between nodal density in contrasted scans and response to cisplatin-based chemotherapy in head and neck squamous cell cancer: a prospective validation.

This prospective study was done to validate an earlier retrospective study demonstrating a relationship between complete response to chemotherapy and nodal density as estimated in contrasted computed tomography (CT scans) in head and neck squamous cell carcinoma (HNSCC). CT scans of 36 patients were evaluated by two radiologists blinded to therapeutic outcome. The density of the largest node (> 2 cm) was compared to that of nuchal muscles. A node was classified as hypodense if more than 33% of the nodal surface area consisted of hypodense zones. Density and nodal staging were related: 67% (10 of 15) of patients with N3 disease but only 29% (six of 21) with N1-N2 exhibited isodensity, p < 0.05. Complete response to chemotherapy was noted in 63% (10 of 16) of the isodense group but only in 15% (three of 20) of the hypodense group, p < 0.01. We believe that nodal density can be used for therapeutic decision-making in high nodal volume HNSCC.

Adult↗
PubMedDate not supplied

cis-Dichlorodiammineplatinum(II) in non-small cell carcinoma of the lung.

The role of cis-dichlorodiammineplatinum(II) (cis-platinum) as a single agent in non-small cell lung cancer has not been clearly defined, and extensive phase II studies have not been conducted. However, objective responses were noted in several early clinical trials. A review of these reports, including combinations with conventional agents, shows 15 partial responses among 100 patients. Results are presented on a new protocol using high-dose cis-platinum with mannitol-induced diuresis combined with cyclophosphamide and Adriamycin. An overall partial response rate of 28% was observed, including a 38% response rate in good performance status patients, with a median survival of 16 months in responding patients. Data from recent combination protocols do not define the activity of cis-platinum as a single agent, but suggest that it may be useful in non-small cell carcinoma of the lung.

Adult↗
PubMedDate not supplied

Vindesine in the treatment of esophageal carcinoma: a phase II study.

Vindesine, a new vinca alkaloid, has shown therapeutic activity in several human malignancies. A phase II study in 26 patients with squamous cell carcinoma of the esophagus was performed. Sixty percent of these patients had received prior chemotherapy. The starting dose was 3.0 mg/m2, which was escalated by 0.5 mg/m2 to a maximum of 4.5 mg/m2. Treatment was given once weekly for 7 weeks and every other week thereafter. Twenty-three patients were evaluable for response and toxicity. One complete remission (3 months), three partial remissions (5, 4, and 2+ months), and two minor responses (1.5 and 1 month) were seen. The major toxic effects were peripheral neuropathy, leukopenia, fever and myalgias, and alopecia. There was one drug-related death from leukopenia and sepsis. Vindesine has demonstrated therapeutic activity in esophageal carcinoma. Further studies with this agent are indicated.

Adult↗
PubMedDate not supplied

CIS-Dichlorodiammineplatinum(II) in the treatment of epidermoid carcinoma of the head and neck.

Twenty-six patients with far-advanced epidermoid carcinoma of the head and neck were treated with cis-dichlorodiammineplatinum(II) (DDP) in high doses, utilizing the technique of concurrent mannitol-induced diuresis. All 26 patients had received prior radical radiotherapy to local disease, 14 had had major ablative surgical procedures, and all but five had been previously treated with chemotherapy. Responses were as follows (duration in months): two complete (2+, 6+), six partial (1, 2, 3, 4, 5+, 8+), ten minor (all but one less than 1.5), and eight no change or progression. Responses were seen in primary tumors, neck nodes, and pulmonary metastases. Nausea and vomiting were seen consistently in all patients but were never dose-limiting. Myelosuppression was mild, with only three patients developing platelet counts less than 50,000/mm3 and no patient with a wbc count less than 2000/mm3. Transient elevations of serum creatinine were common but no patient developed peak levels greater than 2 mg/dl. Transient tinnitus was also common although only four patients developed clinically significant hearing loss during the trial and DDP could be definitely implicated in only one instance. DDP in this dose and schedule is thus effective and safe therapy in a very heavily pretreated group of patients with advanced head and neck cancer and is now being used in combination with other agents in the initial treatment of these patients.

Aged↗
PubMedDate not supplied

Final report of a phase II study of chemotherapy with bleomycin, epirubicin, and cisplatin for locally advanced and metastatic/recurrent undifferentiated carcinoma of the nasopharyngeal type.

PURPOSE: This article presents an assessment of the combination of bleomycin, epirubicin, and cisplatin as induction chemotherapy before radiotherapy in the treatment of undifferentiated carcinoma of the nasopharyngeal type in patients with recurrent/metastatic disease (group A), and in previously untreated patients with locoregionally advanced disease (UICC-AJCC 87, N2-3, M0) (group B) in terms of toxicity, antitumoral activity, and therapeutic efficacy. PATIENTS AND METHODS: From January 1987 to September 1990, 111 consecutive patients with histologically proven UCNT were treated with six cycles of intravenous cisplatin (100 mg/m2 day 1) epirubicin (80 mg/m2 day 1), and bleomycin (15 mg bolus day 1), followed by 16 mg/m2/day continuous infusion for 5 days, repeated every 21 days for three cycles. Three further cycles without bleomycin were given to 44 patients in group A. In group B (67 patients), only three cycles of the same protocol were given, with a slightly lower dose of epirubicin (70 mg/m2), followed by conventional radiotherapy (70 Gy/7 weeks). RESULTS: Of 44 patients entered in group A, 38 were evaluable for response. We observed 9 (20%) complete responses and 11 (25%) partial responses, for a 45% overall response rate. In 12 patients not previously given chemotherapy, there were 4 complete responses, compared to 5 complete responses in 32 patients previously treated with chemotherapy. Four patients are alive with no evidence of disease after 53+, 60+, 61+, and 72+ months. In group B the overall response rate to chemotherapy was 98% with 42 complete (62%) and 24 partial responses (36%). Three months after the end of radiotherapy, the overall complete response rate was 94% (63 patients). After a median follow-up time of 77 months (range, 53-94), the 4-year overall survival and disease-free survival rates for this group are 66% and 60%, respectively. The median disease-free survival has not been reached at 90 months. CONCLUSION: The results of the BEC combination trial are very encouraging in metastatic and recurrrent UCNT, with durable remissions in this poor-prognosis population. The results in patients with locally advanced disease have motivated prospective phase III testing of the neoadjuvant chemotherapy approach to evaluate its impact on locoregionally advanced disease (> or =N2MO UICC-AJCC 87).

Adolescent↗