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Biomedical subjects

G B Ciottoli

Publications and source records attributed to G B Ciottoli.

14 recordsLinked to original sources
PubMed1994

Double-blind randomized study of lonidamine and radiotherapy in head and neck cancer.

PURPOSE: Preclinical studies showed lonidamine to potentiate the effects of x-irradiation by inhibiting the repair of potentially lethal damage. This Phase III double blind, placebo-controlled study was performed to evaluate whether lonidamine can increase the tumor control of radiotherapy in the treatment of advanced head and neck cancer without any synergistic toxic effects on the exposed normal tissues. METHODS AND MATERIALS: Ninety-seven patients with Stages II-IV squamous cell carcinoma of the head and neck were enrolled. Separate analyses were done on the 96 eligible patients and the 90 patients who completed the prescribed treatment regimen. Patients received radiotherapy up to a planned total of 60-66 Gy, in 2 daily fractions of 1.5 Gy each and either lonidamine (450 mg p.o. in three divided daily doses) or placebo, given continuously for 3 months or up to 1 month after the end of radiotherapy. RESULTS: The rate of tumor clearance was 66% (32/48) in the lonidamine group and 65% (31/48) in the placebo group, while the subsequent failure rate was 50% and 77%, respectively (p < 0.05). The 3 and 5 year locoregional control rates in the adequately treated patients achieving complete tumor clearance were 66% and 63% for lonidamine vs. 41% and 37% for placebo. The disease-free survival in adequately treated patients was significantly better in the lonidamine group (p < 0.03), with 3 and 5 year rates of 44% and 40%, respectively, vs. 23% and 19% in the placebo group. The overall survival rate for all eligible patients at both 3 and 5 years was 44% in the lonidamine group and 44% and 31%, respectively, in the placebo group. Both acute and late radiation reactions were similar in the two groups. Myalgia and testicular pain were the most frequent side effects of lonidamine with an incidence of 8.5% and 4.2%, respectively. CONCLUSION: The addition of lonidamine to hyperfractionated radiotherapy was correlated with a statistically and clinically significant proportion of long-term disease-free patients. The toxicity of radiotherapy was not aggravated by the drug and the overall tolerance of the combined regimen was acceptable.

Aged↗
PubMed1990

Phase II study of lonidamine in non-small cell lung cancer: final report.

Lonidamine (LND) is a new anti-cancer drug which interferes with the energy-yielding processes of tumour cells without affecting DNA replication. A total of 69 previously untreated patients with non-small cell lung cancer (NSCLC) entered this study. LND was given orally as a single agent at doses ranging from 450 to 900 mg day-1 until tumour progression (2 to greater than or equal to 1,402 days). Partial responses (PR) occurred in 7/69 patients (10.1%); 4/25, 1/27 and 2/9 for epidermoid, adenocarcinoma and large cell cancer respectively. PR by stage was 4/10, 1/3, 1/20 and 1/28 for stages I, II, III and IV, respectively. The median duration of response was 303 days (greater than or equal to 61 to greater than or equal to 338 days). The median survival for the whole group was 261 days. Toxicity was assessed in all patients. No myelosuppression occurred. The main side-effects were myalgia (68%), loss of appetite (23%), asthenia (20%) and testicular pain (13%). Doses above 450 mg day-1 produced more severe side-effects without any improvement in therapeutic activity.

Adenocarcinoma↗
PubMed1989

The potential role of lonidamine (LND) in the treatment of malignant glioma. Phase II study.

Up-to-date unsatisfactory results obtained in multimodality treatments of malignant glioma have prompted the research of new therapeutic modalities with 'unconventional' modes of action. Lonidamine (LND) is a drug which reduces aerobic glycolytic activity in both human and experimental tumors. This effect mainly depends on the inhibition of mitochondrially-bound hexokinase (HK) which is present in large amounts in malignant cells. A Phase II study was conducted on patients with recurrent glioma; 12 patients were admitted to the study. Clinical side effects were moderate, necessitating a reduction of the dosage in only 1 case. The objective results were evaluated according to the indications of Levin. 2 responders and 3 cases of stable disease were observed out of 10 evaluable patients. The potential value of this new drug is discussed.

Adolescent↗
PubMed1989

Phase II study of lonidamine in metastatic breast cancer.

Thirty patients with previously treated metastatic breast cancer were entered in a phase II study with oral lonidamine. Twenty-eight patients are evaluable for toxicity and 25 for response. A partial remission was obtained in four patients (16%) and disease stability in 11 (44%): 10 patients progressed (40%). Toxicity was acceptable, consisting mainly of myalgias (39% of patients) and asthenia (21.4%). No myelotoxicity was observed. The drug is active in previously treated metastatic breast cancer and, because of its peculiar pattern of action and toxicity, deserves to be evaluated in combination with cytotoxic chemotherapy.

Adult↗
PubMed1988

Chemotherapy/radiation therapy plus/minus lonidamine in the treatment of non-small cell lung cancer (limited disease): preliminary results.

One hundred sixteen patients with unresectable locally advanced non-small cell lung cancer (NSCLC) were accrued in a prospective randomized trial comparing (A), chemotherapy (cisplatin and etoposide [VP-16]) for two courses plus radiation therapy (30 + 20 Gy split course), followed by an additional two courses to (B), the same regimen plus the addition of lonidamine (LND). There were 93 patients evaluable for response (46 in the chemotherapy/radiation arm and 47 in the chemotherapy/radiation/LND arm). One hundred fifteen patients were evaluable for toxicity. The overall response rates, median time to progression, and median survival time were similar in both arms. For the group of patients with squamous cell histology, time to progression was 27 weeks on arm A and 38 weeks on arm B (P = 0.01). Two-year survival in the squamous cell group in arm A was 9%, in arm B, 39%. LND does not give rise to additional toxicity, although myalgia and testicular pain are characteristic side effects.

Adult↗
PubMed1987

Phase II double-blind randomized study of lonidamine and radiotherapy in epidermoid carcinoma of the lung.

Patients with non metastatic squamous cell lung cancer were treated with radiotherapy (RT) plus lonidamine (LND) or placebo (PLAC), according to a randomized double-blind study design. Treatment with lonidamine 150 mg t.i.d. (27 patients) or placebo (23 patients) started 3 days before RT, lasted up to 7 months. Partial responses were observed in 14 and 6 patients respectively in the LND + RT and PLAC + RT groups. Statistical analysis of the survival curves showed no significant difference between the LND + RT (median 311 days) and PLAC + RT (median 193 days) groups. Stage III patients survived significantly longer (p less than 0.05) when treated with LND + RT (median 318 days) than with PLAC + RT (median 163 days). No synergistic toxic effects between radiation and LND were noted. To confirm these data a new and larger multicentric study is now in progress.

Aged↗
PubMed1987

Proposed evaluation scale for damage to healthy tissues as a result of radiotherapy of chest, head and neck cancers.

The authors present, as a criterion of side-effect damage, an evaluation scheme based on the qualitative grading of the acute, intermediate and late effects of the therapeutic irradiation of chest, head and neck cancers. The choice of individual qualitative clinical criteria is complex and arbitrary, although the parameters used are currently found in the literature on radiotherapy. Nevertheless the classifications they have proposed, applied clinically in cases of head and neck cancers, have proved useful in assessing the risk factors of acute and late radiation effects according to the doses delivered. The gradings here described constitute a useful tool for the preliminary assessment of radiation damage and will facilitate the comparative analysis of different case series.

Evaluation Studies as Topic↗
PubMed1984

Early observations on the administration of Lonidamine in cancer patients.

Lonidamine was studied in advanced cancer patients. The drug was given orally by single or repeated administrations. Single doses ranged from 150 to 450 mg. Repeated administrations were performed with progressively increasing doses: 450-900 mg daily. Lonidamine lacked severe toxic effects after both single and prolonged administrations. The most common side effect was myalgia; gastrointestinal discomfort was also reported. 1 patient with lung cancer experienced an episode of arrhythmia which subsided upon discontinuation of treatment and did not reoccurr++ when treatment was reinstated. 1 partial and 2 minor responses were observed in the 6 patients with breast cancer.

Adult↗
PubMed1984

Phase II study of lonidamine in inoperable non-small-cell lung cancer.

31 patients with inoperable non-small-cell lung cancer were treated with Lonidamine at daily doses of 450-900 mg orally. Side effects mostly consisted of myalgias, often severe, and gastrointestinal symptoms. Lonidamine was discontinued in 8 patients because of tumor progression and in 2 on account of side effects. 3 partial responses were observed, 2 in patients with epidermoid tumors.

Aged↗
PubMed1984

Lonidamine plus adriamycin versus adriamycin alone in the adjuvant treatment of recurrent papillary carcinomas of the urinary bladder.

This paper reports the interim results of 25 patients included in a double-blind study in which the combination of Lonidamine plus adriamycin is compared to adriamycin alone in the adjuvant treatment of papillary carcinomas of the urinary bladder. Although it is impossible to draw any conclusion at this time on the therapeutic activity of this combination, tolerance was judged satisfactory.

Adult↗
PubMed1984

Lonidamine and radiotherapy in head and neck cancers. A pilot study.

The tolerance and antitumor activity of Lonidamine combined with radiotherapy were studied on 40 patients with head and neck cancer and compared with a historical control group. Lonidamine was well tolerated. 26 and 17 complete responses were seen in the Lonidamine-treated group and in the historical control group, respectively.

Antineoplastic Agents↗
PubMed1979

N-Methyl-benzylamine, a metabolite of pargyline in man.

1. N-methyl-benzylamine was identified in human urine and plasma after the administration of pargyline in man. This metabolite was identified by thin layer chromatography mobility, gas chromatographic retention time and mass spectrum relative to authentic N-methyl-benzylamine. 2. [14C]-N-methyl-benzylamine, together with a small amount of [14C]-benzylamine, was formed in vitro from [14C]-pargyline when this was incubated with human and rat liver microsomes. 3. The urinary excretion rates of pargyline and its metabolite have also been described.

Adult↗
PubMed1979

[Structure and antipyretic-hypothermizing effect of various pyrazol/1,5-a/pyrimidines].

Structures of condensation products between 3-phenyl-5-aminopyrazole and ethyl ethoxymethylenacetoacetate and ethyl acetonoxalate are demonstrated, namely ethyl 2-phenyl-7-methylpyrazolo[1,5-a]pyrimidin-6-carboxylate and ethyl 2-phenyl-7-methylpyrazolo[1,5-a]pyrimidin-5-carboxylate. Studies on antipyretic and hypothermizing activity of the acid derived from the latter and of other compounds are reported.

Animals↗