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M Marangolo

Publications and source records attributed to M Marangolo.

At least 73 records · Page 4Linked to original sources
PubMed1991

Different effects of sequential combinations of N-methylformamide with 5-fluorouracil on human colon carcinoma cells growing in nude mice.

The effects of the combination of N-methylformamide (NMF) with 5-fluorouracil (5-FU) on tumor growth and morphological features of human colon carcinoma cells (HT29) implanted in nude mice were assessed. Both agents were administered i.p. at tolerable doses: 5-FU at 19 mg/kg for 5 days and NMF at 200 mg/kg for 12 days. Four main schedules were tested: 5-FU alone, NMF alone, NMF followed by 5-FU and 5-FU followed by NMF. The last sequence was the most effective, as compared with the other treatment regimens. In particular, the 5-FU----NMF combination induced a tumor inhibition of about 75% at the end of the treatments (17th day) versus an inhibition of 23%-43% in the other schedules. Morphological observations, carried out by light and electron microscopy, indicated a possible relationship between the presence of structural changes and tumor growth inhibition. The results of this study renew interest in the use of NMF in sequential combination confirming sequence as a critical factor for the optimal combination of NMF and 5-FU.

Adenocarcinoma↗
PubMed1991

Oral ondansetron (GR 38032F) for the control of CMF-induced emesis in the outpatient.

The efficacy of the serotonin antagonist ondansetron (GR 38032F) was evaluated in the prevention of nausea and vomiting induced by CMF chemotherapy in 29 breast cancer patients. At their first treatment course of CMF, all given IV on day 1 q 21 days, patients were given oral antiemetic treatment as follows: ondansetron 8 mg, 2 h prior to CMF, repeated after 5 and 10 h the day of chemotherapy and then 8 mg tds for a minimum of 3 days to a maximum of 5 days following chemotherapy. At first course of CMF, complete protection from emesis and nausea was observed in 86.2% and 62% of patients, respectively. At subsequent CMF courses with ondansetron, complete control of emesis was observed in 80% of patients. Side effects were mild and no dystonic reactions were observed. Ondansetron represents an effective, safe, and easily administered outpatient regimen. The addition of a corticosteroid to ondansetron could further improve control of CMF-induced emesis.

Administration, Oral↗
PubMed1991

Treatment of metastatic colorectal cancer by means of specific monoclonal antibodies conjugated with iodine-131: a phase II study.

Eighteen consecutive patients with advanced and/or metastatic colorectal carcinoma have been treated with intraperitoneal administration of radiolabelled (iodine-131) monoclonal antibodies raised against different antigens associated to these kinds of tumours: anti-CEA FO23C5, anti-CEA BW494/32, anti-TAG B72.3, AUA1. The doses of isotope ranged between 21 and 150 mCi (777-5550 MBq) which delivered a radiation dose to the target tumour from 768 to 4628 cGy. Thirteen patients were previously treated with conventional regimens which consisted of chemotherapy (5-fluoracil with or without other anti-neoplastic drugs) both in adjuvant or palliative setting. Three patients are considered non-evaluable owing to concomitant chemotherapy in 2 and lack of objective parameters in 1. Out of 15 evaluable patients 2 achieved complete remission and 2 partial remission with a response rate of 26.6%. Three stable and 8 with progressive disease have also been registered. The toxicity was negligible consisting of hematologic WHO grade 1 in 7 patients, grade 2 in 1 patient and grade 3 in 1 patient, as well as hepatic WHO grade 1 in 8 and grade 2 in 2 patients. The authors conclude that this innovative way of treatment for advanced colorectal carcinoma seems to offer promising therapy; from these data, therefore, a new trial is justified employing radiolabelled MoAbs in well selected patients with metastatic or locally advanced colorectal carcinoma.

Adenocarcinoma↗
PubMed1991

Importance of cell cycle perturbations on the effectiveness of N-methylformamide and anti-neoplastic drugs in combination.

The effect of N-methylformamide (NMF) in combination with Adriamycin (ADM) and cis-diamminedichloroplatinum (DDP) on the cell survival and cell cycle kinetics of two human tumour lines was assessed: HT29 colon carcinoma and M14 melanoma cells were exposed to ADM and DDP alone or in combination with a non-cytotoxic dose of NMF, according to different schedules. The results demonstrate that NMF exposure sensitized both tumour cell lines to the lethal activity of ADM and DDP; however, reverse sequences had to be applied to reach an increase in the lethal activity of the two different drugs. The ADM-NMF combination determined a powerful decrease in the surviving fraction of the two cell lines when ADM was given as the first agent (ADM----NMF), while the reverse sequence did not increase the ADM cytotoxic effect. With respect to the DDP-NMF association, the sequence which accounted for a greater sensitizing effect was NMF administration followed by DDP treatment (NMF----DDP). This work demonstrates the importance of timing in combined treatments which involve NMF. A delay in cell proliferation elicited by NMF exposure could be responsible for the effectiveness of the combined treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Prevention of cisplatin-induced emesis: a double-blind multicenter randomized crossover study comparing ondansetron and ondansetron plus dexamethasone.

Ondansetron (OND) is a new 5-HT3 receptor antagonist that give complete protection from emesis/nausea in approximately 50% of cisplatin (CDDP)-treated patients. To evaluate if dexamethasone (DEX) added to OND increases antiemetic efficacy, we carried out a double-blind randomized crossover study to compare the antiemetic activity of OND with OND plus DEX. One hundred two chemotherapy-naive patients (44 women and 58 men) scheduled to receive CDDP chemotherapy at doses greater than or equal to 50 mg/m2 entered the study. Eighty-nine patients completed both cycles with the following results: complete protection from emesis/nausea was obtained in 57/59 patients (64.0%/66.3%) with OND and in 81/79 (91.0%/88.8%) with OND plus DEX (P = .0005/P = .0021). At the end of the study, 53% of the patients expressed a treatment preference, and of these, 74% chose OND plus DEX compared with 26% who preferred OND alone, a statistically significant difference (P less than .003). Side effects were very mild and not significantly different between the two treatments. We conclude that OND plus DEX is more efficacious than OND in protecting patients from CDDP-induced emesis and nausea.

Antiemetics↗
PubMed1991

High dose chemotherapy with carboplatin, VP 16 +/- ifosfamide in germ cell tumors: the Italian experience.

This schedule has shown an interesting activity with nearly 40% of the patients achieving CR. Moreover 4 patients experienced an inversion rate (CR with ABMT when they never achieved this status before). In terms of toxicity, this schedule seems feasible with 2/28 toxic deaths, which is in the lower part of the range of major solid tumors ABMT programs. But even if the rationale is proper, a better patients' selection is required. The CCR (continuous Complete Remission) rate is overimposable to other main studies previously published, but all our CCR were obtained in responding patients (Sensitive Relapses or unresectable PR). We may suggest that earlier transplantation is advisable when less tumor bulky is present and less clonal eterogeneity. The exact maximum tolerated dose of Carboplatin/VP 16/Ifosfamide programs has not yet clearly pointed out. The lack of major life-threatening episodes and neuro/nephrotoxicity may allow us to explore higher Carboplatin doses. Anyway the ultimate answer to the utility of ABMT trials must come from a randomized study in responding patients.

Adult↗
PubMed1991

Neoadjuvant chemotherapy for nonmetastatic osteosarcoma of the extremities.

Between September 1986 and December 1988, 125 patients with osteosarcoma of the extremities entered the second neoadjuvant study at the authors' institution. Patients received preoperatively two cycles of methotrexate (MTX) intravenously, followed by cisplatinum (CDP) intraarterially, plus adriamycin (ADM) intravenously. After surgery, the patients classified as "good responders" (more than 90% tumor necrosis) received ADM, MTX, and CDP, while the "poor responders" (less than 90% tumor necrosis) had a longer chemotherapy that included ifosfamide and etoposide (VP-16) in addition to MTX, ADM, and CDP. Limb salvage was possible in 85% of patients, 8% had an amputation, and 7% had a rotationplasty. The surgical margins were adequate (radical or wide) in 88% of cases and inadequate (marginal or intralesional) in 12%. At an average follow-up period of 28 months (range, 13 to 41), 109 patients (87%) remained continuously disease free, 15 (12%) relapsed with pulmonary metastases, and one patient (0.8%) had a local recurrence. Compared with the first neoadjuvant study at the authors' institution that used only MTX and CDP preoperatively, the percentage of limb salvages, "good responders," and continuously disease-free survival at two years was significantly higher in the second Rizzoli neoadjuvant study (85%, 74%, and 87% versus 77%, 52%, and 59%). Systemic toxicity because of chemotherapy was superimposable. A retrospective analysis of the real dose intensity for each patient demonstrated a correlation between the intensity of chemotherapy and prognosis.

Adolescent↗
PubMed1990

Mitoxantrone (M) and vinblastine (V) in the treatment of advanced breast cancer.

Twenty-four patients with metastatic breast cancer, all but 1 pretreated with one or more chemotherapeutic regimens, were entered in a pilot study to assess toxicity and efficacy of the combination mitoxantrone and vinblastine. Dominant sites of metastases were viscera in 9 patients, bone in 10 and soft tissues in 5. All patients received mitoxantrone 10 mg/m2 i.v. on day 1 and vinblastine 1.7 mg/m2 by 4 hour infusion on days 3, 4 and 5, every 3-4 weeks. Objective responses (1 CR, 7 PR) were observed in 8 (38%) of the 21 evaluable patients. Median duration of response was 10.5 months. Of 12 patients pretreated with an anthracycline containing regimen, 4 responded (1 CR and 3 PR). Major toxicity was myelosuppression, grade 4 in 2 cases and grade 3 in 2 others. No evident alopecia was observed and only 1 case of grade 1 cardiac toxicity. In conclusion, mitoxantrone followed by vinblastine is an effective regimen in metastatic breast cancer also in pretreated patients, and previous anthracycline administration does not seem to reduce the percentage of response. Moreover, toxicity is generally mild.

Adult↗
PubMed1990

Ondansetron (GR38032) in the prophylaxis of acute and delayed cisplatin-induced emesis.

Sixty five chemotherapy naive patients receiving cisplatin (50-120 mg/m2) containing chemotherapy participated in an evaluation of ondansetron, a 5-HT3 receptor antagonist, in the prophylaxis of acute and delayed nausea and emesis. Ondansetron was given as three 0.15 mg/kg doses intravenously (0.5 h before, 3.5 h and 7.5 h after cisplatin) for acute emesis followed by 8 mg orally 8-hourly for five days at 24 h post-cisplatin for delayed emesis. For acute emesis (first 24 h, n = 63), complete control was achieved in 34 patients (54%) and major control (1-2 episodes) in 16 patients (25%). Complete protection from acute nausea was achieved in 48 patients (76%). For delayed emesis (days 2-6, n = 55), 33 patients (60%) were completely protected or reported one to two episodes during the entire 5-day observation period; 63% reported only mild or no nausea. Ondansetron was well tolerated with no significant drug-related adverse events. These results are consistent with serotonin being a significant transmitter of cisplatin-induced emesis.

Acute Disease↗
PubMed1989

Adjuvant chemotherapy with fluorouracil and CCNU in colon cancer. Results of a multicentric randomized study.

To establish the effectiveness of adjuvant chemotherapy in patients with colon cancer after radical surgery, from 1980 to December 1983, 263 patients were randomized in a multicentric study to no further treatment (131 patients) or to a combination of fluorouracil (5-FU) (400 mg/m2 i.v., days 1-5) and lomustine (CCNU) (100 mg/m2 per os on day 5) every 6 weeks for 9 cycles (132 patients). The two groups were well balanced for age, sex, histology, tumor and nodal extent. Chemotherapy was not given to 30 of the 132 randomized patients, and of 98 treated patients only 38 completed the entire protocol. Analysis, as intention to treat, at 54 months did not show any significant difference between the two treatment groups in terms of relapse-free survival (surgery alone, 74.5%; surgery + adjuvant chemotherapy, 70.9%; p = 0.91). In contrast, a significant difference was observed in overall survival (surgery alone, 78.8%; surgery + adjuvant chemotherapy, 60.8%; p = 0.04). The sites of relapse were identical in the two treatment arms. In conclusion, from this study it appears that adjuvant chemotherapy with 5-FU and CCNU seems to have no efficacy in the cure rate of colon cancer patients.

Aged↗
PubMed1989

Depression and abnormal illness behavior in cancer patients.

Evaluation of the incidence of depression among cancer patients has been the object of a number of studies. Recent reports of medically ill patients have indicated that depression is related to several dimensions of abnormal illness behavior (e.g., hypochondriasis, irritability, denial, disease conviction). To investigate the relationship between depression and abnormal illness behavior in cancer patients, a study was conducted of 196 patients with a recent diagnosis of cancer and with a good performance status (Karnofsky score greater than 80). The Hamilton Depression Rating Scale (HDRS) and the Illness Behavior Questionnaire (IBQ) were administered in their validated Italian forms. A cutoff point of 17 on the HDRS revealed 38.26% of the patients as having symptoms of depression, whereas a more conservative cutoff point of 21 indicated a depressive state in 23.97% of the patients. Depressed patients had higher scores on all the IBQ dimensions except that of psychologic versus somatic perception of illness. The results were confirmed by the correlation between the parameters. Higher levels of denial were reported by females and by patients receiving adjuvant or palliative chemotherapy, who had, however, lower levels of dysphoria than patients not receiving treatment. Higher levels of irritability were shown in hospitalized patients. No relationship was found between medical status variables (Karnofsky score, tumor status, and disease extent) and psychologic measures, except for denial. The findings seem to confirm the importance of assessment of depression and illness behavior in cancer patients and suggest the need for more thorough investigation of the psychosocial variables associated with them.

Adult↗
PubMed1989

Locoregional immunotherapy of human ovarian cancer: preliminary results.

Ten patients with advanced ovarian carcinoma (5 in FIGO stage III and 5 in stage IV), following the failure of repeated chemotherapy courses, were submitted to i.p. radioimmunotherapy (RIT). Several antibodies (HMFG1, HMFG2, H17E2, B72.3) were employed. The antibody choice was made on the basis both of immunohistochemistry and immunoscintigraphy results. The mean dose administered in each single course was 17 mg, 3 patients underwent two treatments and 2 patients were injected three times. The isotope employed was 131I (mean dose 92 mCi). The early or late untoward effects were negligible. All patients developed anti-mouse antibodies (HAMA) which reduced, during the further RIT, the MoAbs' effective half-life. The estimated radiation dose delivered to the tumour ranged from 2910 to 11,000 cGy. Both wholebody and liver radiation burden resulted in tolerable limits while the thyroid irradiation was high. In 3 patients the RIT result was ineffective; in 2 cases a temporary ascitis staunch was obtained. In 2 cases the tumour growth was slower than expected and in 3 patients instrumental evidence of partial tumour reduction, still lasting after 4-11 months, was observed.

Antibodies, Monoclonal↗
PubMed1989

Unusual malignant tumours in 49 patients with HIV infection.

Between December 1986 and December 1988, the Italian Cooperative Group on AIDS-Related Tumours documented 49 HIV-related tumours other than malignant lymphomas (ML) and Kaposi's sarcomas (KS), predominantly among HIV-infected intravenous drug abusers (IVDA). Of 12 germinal testicular tumours collected, six were seminomas, two of which were pure embryonal and the other four embryonal mixed. Cervical carcinoma was observed in nine IVDAs (intraepithelial in eight and advanced, with rapid progression, in one). Lung cancer associated with HIV infection was reported in eight patients, of whom four had an adenocarcinoma, two a small cell carcinoma, one an epidermoid carcinoma and one a mesothelioma. All patients with non-small-cell-lung cancer (SCLC) were at stage III, while those with SCLC and mesothelioma had limited disease. Five out of eight presented with limited disease at onset. The median age was low; lung cancer occurred predominantly in young adults, of whom all but one were smokers. Three patients could not be treated; four died while on treatment because of progression of the neoplasia and one died of an overdose. Acute lymphoblastic leukaemia (ALL) was diagnosed in five patients. The immunophenotype was always Burkitt-like (L3), and acute myeloblastic leukaemia (M2) was diagnosed in one. Of the central nervous system (CNS) tumours, two cases of glioblastoma and one of medulloblastoma were described. Two cases of young adults with multiple myeloma and two cases of colorectal carcinoma were also reported. One case of chronic lymphocytic leukaemia, one anorectal carcinoma, one oral carcinoma, one pancreatic carcinoma, one thymoma, one kidney carcinoma, one malignant melanoma and thyroid carcinoma were also found.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1989

High-dose etoposide and autologous bone marrow transplantation as intensification treatment in small cell lung cancer: a pilot study.

A pilot study was conducted in which 15 patients with small cell lung cancer (SCLC) with limited or extended disease were treated with high dose etoposide (600 mg/m2 daily for 3 consecutive days) followed by autologous bone marrow transplantation (ABMT). Twelve patients underwent a double graft. All had achieved complete or partial remission with conventional induction chemotherapy (adriamycin and etoposide, plus cisplatin in five cases). After ABMT six of the 15 patients did not receive radiotherapy to the chest; all but four patients received prophylactic brain irradiation. No toxic deaths were recorded during the period of aplasia. Eleven patients relapsed and died after ABMT. The median time to death was 18 months. One other patient died at 13 months of unknown cause. At the present time three patients are alive and free of disease at 54, 51 and 47 months respectively. This pilot study shows that high dose etoposide and ABMT is well tolerated as late intensification for responsive SCLC. Definite conclusions about its precise role in therapy cannot yet be drawn.

Adult↗
PubMed1988

Modulation of the cytotoxic effect of 5-fluorouracil by N-methylformamide on a human colon carcinoma cell line.

The cytotoxic effect of the combination of N-methylformamide (NMF) with 5-fluorouracil (5-FU) on cell survival of the human colon cancer line HT29 was assessed. The differentiating activity of NMF was evidenced by morphological maturation and conversion of cell culture characteristics to those consistent with a more benign phenotype. In combination experiments, the noncytotoxic concentration of 1% NMF was chosen and doses of 5-FU ranging from 5 to 25 micrograms/ml were employed. Two main schedules were tested either on exponentially or stationarily growing cells: (a) 1% NMF for 72 h followed by 12-h exposure to 5-FU; (b) 5-FU for 12 h followed by 72-h exposure to 1% NMF. The results obtained demonstrated that the 5-FU----NMF sequence determined a powerful reduction in the surviving fraction of HT29 cells, while the reverse sequence did not increase the killing effect of 5-FU given alone. Immunocytochemical and scanning electron microscopy studies seemed to confirm that the association in which the differentiating agent followed the 5-FU treatment strongly impaired cellular integrity and function and that cytoskeletal elements, particularly microfilaments, and surface structures could play an essential role in the mechanisms of cytotoxicity. Furthermore, the results of this work indicate that drug sequence is a critical factor for the optimal combination of 5-FU and NMF.

Adenocarcinoma↗
PubMed1987

Applicability of local hyperthermia as adjuvant to systemic chemotherapy.

With the aim of verifying the in vivo applicability of local hyperthermia combined with chemotherapy, 13 patients with superficial metastases from different histologic types of carcinoma, mostly from head and neck cancer, were entered in a pilot study. The chemotherapeutic regimen was cis-platinum, 20 mg/m2/d X 5 days, bleomycin, 10 mg/m2 on days 8 and 12, methotrexate, 100 mg/m2 on day 15, followed after 24 by folinic acid. Hyperthermia, using a microwave apparatus, and chemotherapy were delivered simultaneously. Objective remissions were achieved in 54% of patients, within the hyperthermia field (1 CR and 6 PR). No serious toxicity was noted. Methotrexate distribution after local hyperthermia was evaluated in 8 patients. Response duration was not gratifying, except for patients successively treated with radiation. In conclusion, the combination of chemotherapy plus local hyperthermia deserves subsequent evaluation as part of adjunctive programs.

Aged↗
PubMed1987

Metastases to the submaxillary gland from breast cancer: case report.

A case of metastases to the submaxillary gland from breast carcinoma is reported. The patient, a 68-year-old female, had been operated for a stage II N+ breast carcinoma 4 years before. She then received six courses of CMF adjuvant program. A literature review is presented concerning the 8 well-documented cases reported.

Aged↗