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Biomedical subjects

C Gridelli

Publications and source records attributed to C Gridelli.

At least 73 records · Page 4Linked to original sources

Chemotherapy with mitomycin C and vinblastine in pretreated metastatic breast cancer.

AIMS: In February 1986 we began a study to test the activity of mitomycin C (12 mg/m2) plus vinblastine (6 mg/m2) on day 1 of a 28-day cycle (MV) as second or third-line chemotherapy for metastatic breast cancer patients. METHODS: As of February 1988 the study was stopped after 26 patients had been enrolled. The median age of the patients was 54 years (range 35-78); all patients were progressive from chemotherapy; 15 (57.7%) patients were treated as second and 11 (42.3%) as third line; 19 (73.1%) patients had received anthracyclines as first (13 patients) or second-line (6 patients) chemotherapy; 18 (69.2%) patients had visceral involvement; 7 (26.9%) had one metastatic site, 11 (42.3%) two sites, 6 (23.1%) three sites and 2 (7.7%) four sites. RESULTS: Overall, 86 cycles were administered, with a median number of 3 cycles per patient. Toxicity was mild; hematologic side effects required discontinuation of treatment in 3 cases. Vomiting occurred in 3 (11.5%) patients, nausea in 5 (19.2%). Moderate neurologic toxicity was recorded in 6 (23%) patients. No complete and 3 partial responses were observed. The objective response rate was 11.5% (exact 95% confidence interval, 2.4-30.1). Responses occurred independently of disease-free interval, dominant metastatic site, response to previous chemotherapy, previous anthracycline and line of treatment; all responses were recorded in patients under 50 years of age. Kaplan-Meier estimated median time to progression and overall survival were 13 and 40 weeks, respectively. CONCLUSION: The MV regimen was well tolerated but showed little activity in pretreated metastatic breast cancer.

Adult↗

Phase I study of epirubicin plus vinorelbine with or without G-CSF in advanced non-small cell lung cancer.

The present phase I study was designed to determine the maximum tolerated dose (MTD) of epirubicin, administered every 3 weeks to patients with advanced non-small cell lung cancer (NSCLC), and combined with a conventional dose of vinorelbine [25 mg/m2 intravenously (i.v.) days 1 and 8] with or without the support of granulocyte-colony stimulating factor (G-CSF). 18 patients entered the study. The patients received the following four dose levels of epirubicin (i.v., day 1): 50 mg/m2 (3 patients) and 60 mg/m2 (6 patients) without G-CSF, 75 mg/m2 (3 patients) and 90 mg/m2 (6 patients) with G-CSF (5 micrograms/kg days 4-6 and 9-15). In the patients treated without G-CSF the MTD of epirubicin was 60 mg/m2 and leukopenia was the dose-limiting toxicity. In the patients treated with G-CSF the MTD was 90 mg/m2, myelotoxicity being the dose-limiting toxicity. We observed 1/3 partial response (PR) with epirubicin at the dose of 75 mg/m2 and 2/6 PR at 90 mg/m2. These results would indicate the usefulness of a phase II study with epirubicin at the dose of 90 mg/m2 in association with conventional dose of vinorelbine with the support of G-CSF in advanced NSCLC.

Aged↗

Neoadjuvant chemotherapy with cisplatin, epirubicin and VP-16 for stage IIIA-IIIB non-small-cell lung cancer: a pilot study.

Twenty patients with stage IIIA-IIIB non-small-cell lung cancer were treated with cisplatin, epirubicin and VP-16 (PEV) neoadjuvant chemotherapy (CDDP, 70 mg/m2, i.v., d 1; EDX, 60 mg/m2, i.v., d 1; VP-16, 100 mg/m2, i.v., d 1-2-3; every 3 weeks). A partial response was obtained in 11 cases (55%), stable disease in 3 cases (15%), and progressive disease in 6 cases (30%). After chemotherapy, 8 (40%) patients, all achieving a partial response, were elegible for surgery: 5 (25%) had a complete resection (4 IIIA and 1 IIIB) and 3 (15%) an incomplete resection. The treatment was well tolerated. These data show that PEV is an active regimen for neoadjuvant chemotherapy in NSCLC and recommend this therapeutic approach for stage IIIA patients.

Adult↗

Mitomycin C and vindesine: an ineffective combination chemotherapy in the treatment of malignant pleural mesothelioma.

Twelve patients with malignant pleural mesothelioma were subjected to mitomycin C (MMC) and vindesine (VDS) chemotherapy (MMC 10 mg/m2, i.v., d 1; VDS, 3 mg/m2, i.v., d 1-8, every 4 weeks). No objective response was obtained; 3 (25%) patients had stable disease and 9 (75%) progression of disease. We conclude that MMC plus VDS is an ineffective combination chemotherapy in the treatment of malignant pleural mesothelioma.

Adult↗

Mitomycin C plus vindesine or cisplatin plus epirubicin in previously treated patients with symptomatic advanced non-small-cell lung cancer.

A total of 40 previously treated patients with symptomatic advanced non-small-cell lung cancer (NSCLC) were subjected to second-line chemotherapy with mitomycin C plus vindesine (MV) or cisplatin plus epirubicin (PE). The 12 patients treated with the MV regimen showed no objective response (OR) or symptom palliation. In the 28 patients who received the PE regimen, we obtained a 25% partial response rate, with amelioration of tumor-related symptoms occurring in 35.7% of cases and improvement in the performance status being noted in 25% of subjects. Both regimens were well tolerated. These data show that the administration of cisplatin-based second-line chemotherapy to patients with symptomatic advanced NSCLC may be useful.

Adult↗

Salvage chemotherapy with CCNU and methotrexate for small cell lung cancer resistant to CAV/PE alternating chemotherapy.

CCNU and methotrexate were employed as salvage treatment in 34 small cell lung cancer patients resistant to CAV/PE alternating induction chemotherapy. In the 33 evaluable patients we observed an objective response rate of 21.2% and 3% complete response; median survival was 4 months with 2 patients alive 18 months from starting salvages chemotherapy. The treatment was well tolerated. CCNU and methotrexate has shown to be a moderately active and tolerable salvage treatment for small cell lung cancer after CAV/PE alternating first-line chemotherapy.

Adult↗

Intensive alternating combination chemotherapy and high dose chest radiotherapy in small cell lung cancer.

Sixty-nine patients, 32 with limited and 37 with extensive small cell lung cancer (SCLC), were admitted to the present study. Patients with limited disease underwent alternating combination chemotherapy consisting of CAV (cyclophosphamide, adriamycin, vincristine) and PE (cisplatin and etoposide) regimens and concurrent high dose thoracic radiotherapy (6,000 cGy); prophylactic brain irradiation (3,000 cGy) was administered to complete responders. Patients with extensive disease received the same alternating chemotherapy but not radiotherapy. In the 25 evaluable patients with limited disease we obtained an objective response (OR) in 80% with a complete response (CR) in 54% and partial response (PR) in 24%, stable disease (SD) in 4% and progressive disease (PD) in 16%. Median duration of response was 9.5 months for CR and 8.5 months for PR. Median survival was 14 months for all patients with 12% long-term survivors. Toxicity was acceptable. In the 32 evaluable patients with extensive disease we observed 65.6% OR with 18.7% CR and 46.8% PR, 9.3% minimal response and 25% PD. Median duration of response was 7 months for CR and 8 months for PR. Median survival was 10 months for all patients. The treatment was well tolerated. Our study did not show a therapeutic advantage for alternating combination chemotherapy in SCLC and failed to show the use of high dose chest radiotherapy in combined modality for limited disease.

Adult↗

Phase II study of mitomycin C, etoposide and vindesine in metastatic stage IV non-small-cell lung cancer.

A total of 72 patients with metastatic stage IV non-small-cell lung cancer (NSCLC) were treated with combination chemotherapy comprising the MEV regimen (mitomycin C, 8 mg/m2 given i.v. on day 1; etoposide, 100 mg/m2 given i.v. on days 1-3; and vindesine, 3 mg/m2 given i.v. on day 1; treatment repeated every 3 weeks). In 65 evaluable patients, the objective response rate was 37% (complete responses, 4.7%; partial responses, 32.3%). The median survival was 7.6 months for all patients. The treatment was very well tolerated. MEV proved to be an active and non-toxic regimen for the treatment of metastatic NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗

Second-line chemotherapy of advanced colorectal cancer with sequential high-dose methotrexate and 5-fluorouracil.

Twenty-five patients with pretreated advanced colorectal carcinoma were subjected to second-line chemotherapy with sequential high-dose methotrexate and 5-fluorouracil. In 20 evaluable patients 2 (10%) partial responses, 12 (60%) stable disease and 6 (30%) progressions were observed. Partial responses were maintained for 3 and 4 months respectively; stable disease had a median duration of 4 months. The overall median survival after progression was 7 months. From our results sequential high-dose methotrexate and 5-fluorouracil cannot be recommended as second-line chemotherapy in advanced colorectal cancer.

Adult↗

Partial response of metastatic hepatocellular carcinoma after treatment with thymostimulin.

We describe a case of partial regression of metastatic hepatocellular carcinoma after treatment with thymostimulin. The patient, a 58-year-old man, received no specific therapy for his tumor, but only a thymus extract ("thymostimulin"). At follow-up 6 months later the patient showed clinical improvement, reduction of alpha-fetoprotein level an liver lesions, and a complete regression of lung metastases. The patient died of progression of the disease with 2-year overall survival.

Adjuvants, Immunologic↗

Clinical trial with 5-fluorouracil and leucovorin.

Many clinical trials with 5-fluorouracil and leucovorin have been reported. This combination therapy seems to play an important role in untreated advanced colorectal cancer. In other neoplasms (gastric, head and neck, breast cancer) further studies are required.

Adenocarcinoma↗

Myocardial ischemia during intravenous prostacyclin administration: hemodynamic findings and precautionary measures.

This study reports coronary and systemic hemodynamics, and metabolic responses to atrial pacing, prostacyclin (PGI2), and iloprost, its stable analogue, in 16 patients with severe coronary obstruction as well as predominant narrowing in the left anterior descending artery. PGI2 caused ischemia in six patients with low anginal threshold during pacing. In three of them ischemia was also precipitated by iloprost. Drugs were infused at therapeutic doses and were discontinued when pain occurred. Angina disappeared promptly (less than or equal to 3 minutes) and spontaneously after the infusion of PGI2, whereas after the analogue it was long lasting (greater than or equal to 5 minutes) and was relieved by 125 mg intravenous aminophylline, an antagonist of dipyridamole-induced coronary dilation. Ischemia was associated with a drug-induced decrease in arterial blood pressure and reflex tachycardia, and occurred despite increased great cardiac vein (GCV) blood flow and decreased resistance, which is consistent with either a failure of regional flow to increase proportionally to the metabolic demand or a subendocardial-subepicardial steal. However, the following findings favor the latter hypothesis: heart rate and rate-pressure product at the onset of pain were lower with drugs than with pacing, and GCV blood flow, measured at a comparable heart rate, was less with pacing than with drugs. In conclusion, PGI2 and analogues may induce ischemia in patients with advanced coronary artery disease. The mechanism appears to be related to a dipyridamole-like maldistribution of flow. Counteraction of ischemia can be achieved by aminophylline.

Cardiovascular Agents↗

Effects of iloprost, a stable prostacyclin analog, on exercise capacity and platelet aggregation in stable angina pectoris.

The effects of iloprost, a chemically stable compound with prostacyclin mimetic activity, on exercise capacity and platelet aggregation were assessed in 24 patients with effort angina and proved critical (at least 70% diameter narrowing) coronary artery disease. Upright bicycle ergometer testing (25-W increments every 2 minutes) was performed during drug and placebo infusions using a crossover, randomized, single-blind protocol. Samples for measurements of adenosine diphosphate-induced platelet aggregation in platelet-rich plasma were obtained in all patients before and during the study. Compared with placebo, intravenous iloprost consistently (p less than 0.001) prolonged exercise duration and time to onset of significant (0.1 mV) ST depression. Angina and ST depression occurred at a greater heart rate and rate-pressure product. Benefits were remarkable in some patients (67%) and not in others. Iloprost administration resulted in reduced platelet aggregation at peak exercise in all patients, whether they had consistent or little response to the drug. Thus, iloprost administration may improve exercise capacity in patients with stable exertional angina pectoris. Improvements are independent of changes in the major determinants of myocardial oxygen demand and associated with markedly reduced platelet aggregation, which may account for increased myocardial perfusion in patients with high sensitivity to coronary constriction.

Angina Pectoris↗

[Opposing effects of propranolol and diltiazem on the angina threshold during an exercise test in patients with syndrome X].

Patients with angina pectoris, exercise induced myocardial ischemia, normal coronary arteries and no evidence of epicardial spasm, i.e. patients with syndrome x, have been suggested to haven inadequate increase in coronary blood flow during tachycardia, possibly due to a functional disorder of small coronary vessels. To evaluate the best medical management of this syndrome we studied 13 patients who showed the above set of findings. Patients were given propranolol (160 mg daily), diltiazem (360 mg daily) and placebo for 2 weeks, using a randomized single blind protocol. Upright bicycle ergometer testing was performed at the end of each period of treatment. Compared to placebo, diltiazem significantly (p less than 0.001) prolonged exercise duration (x +/- SD: 365 +/- 86 vs 303 +/- 89 sec) and time to onset of angina (358 +/- 88 vs 276 +/- 90 sec). Angina appeared in 7 patients with diltiazem vs 13 patients with placebo and occurred at a higher rate pressure product (26.3 +/- 3.5 vs 24.1 +/- 2.8 X 10(-3); p less than 0.02). Conversely, following propranolol exercise duration and time to onset of angina were unchanged and angina appeared in all patients at a lower rate pressure product (18.3 +/- 2.9 vs 24.4 +/- 3.6 X 10(-3); p less than 0.001). The most likely explanations for these findings are: propranolol counteracts beta 2-adrenergic receptors, thus further reducing coronary reserve. This may lower the anginal threshold; Diltiazem reduces smooth muscle tone in small coronary vessels. This may result in increased coronary reserve and exercise duration.

Adult↗