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Biomedical subjects

D Giannarelli

Publications and source records attributed to D Giannarelli.

At least 91 records · Page 5Linked to original sources
PubMed1991

Fluorouracil, doxorubicin, and cyclophosphamide versus fluorouracil, doxorubicin, and cyclophosphamide plus lonidamine for the treatment of advanced breast cancer: a multicentric randomized clinical study.

Experimental models have demonstrated the Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH)-potentiating activity of lonidamine. Phase II clinical trials on advanced breast cancer have shown that this drug induced a 16% objective response rate. Present multicentric randomized trial was conducted to verify whether lonidamine can potentiate the antineoplastic effects of conventional fluorouacil, Adriamycin, cyclophosphamide (FAC) chemotherapy in advanced breast cancer. From January 1987 to December 1989, 265 patients were enrolled in this study, and 231 are evaluable for response. After stratification according to institution and ECOG performance status (PS), the patients were randomly allocated to receive either standard FAC therapy (group A) or FAC plus lonidamine (600 mg orally daily three times a day) (group B). After three FAC courses, the patients with no progressive disease were further randomized to either receive continuous treatment up to the time of tumor progression (maximum: 10 courses) or to discontinue therapy when a response "plateau" was reached. In this latter group, the same therapy was restarted at relapse or disease progression. Objective response (complete response plus partial response) was significantly higher in group B (66.3%) compared to group A (42.3%). The actuarial median times to disease progression was also significantly longer (P less than 0.0001) in group B (median 9 months) than in group A (median 6 months). Other than myalgia and gastric pain, no increased toxicity was observed in the lonidamine. The analysis of second randomization are yet available because of the longer follow-up time required. Present findings suggest an interesting additive effect of lonidamine when combined with FAC chemotherapy and warrant further investigation in other therapeutic regimens and in other neoplastic diseases.

Adult↗
PubMed1990

High serum IL-2 levels are predictive of prolonged survival in multiple myeloma.

In this study we analysed serum IL-2 levels in 61 patients with multiple myeloma (MM). Patients serum IL-2 levels were significantly higher than normal controls. Moreover, higher serum IL-2 levels were associated with a prolonged actuarial survival. In particular, 87% of the MM patients with IL-2 greater the or equal to 10 U/ml are still alive at 5 years while only 13% of the remaining patients with IL-2 less than 10 U/ml are alive. The multivariate analysis confirmed these data indicating that high serum IL-2 levels are the most useful predictor index of longer survival in MM patients. Furthermore, among the 50 patients in whom serum beta-2-microglobulin (SB2M) determination was available we observed that all patients with serum IL-2 levels greater than or equal to 10 U/ml had SB2M less than 6 micrograms/ml, whereas in patients with serum IL-2 less than 10 U/ml SB2M ranged from 1.3 to 15 micrograms/ml. Using these two parameters we were able to identify three groups of patients with different survival duration. Group A (9 patients) defined by serum IL-2 greater than or equal to 10 U/ml and SB2M less than 6 micrograms/ml in which all patients are alive: group B (26 patients) characterized by serum IL-2 less than 10 U/ml and SB2M less than 6 micrograms/ml in which 24% of patients are alive and group C (15 patients) characterized by serum IL-2 levels less than 10 U/ml and SB2M greater than or equal to 6 micrograms/ml in which the actuarial survival curve drops to 0 at 2.5 years. A statistically significant difference was observed between groups A and B (P less than 0.05), groups A and C (P less than 0.01) and groups B and C (P less than 0.01). These data could reflect the existence of an active T cell control on B cell neoplasia and may suggest the opportunity of a more extensive use of recombinant biological modifiers such as IL-2 in the therapeutic strategy of MM.

Adult↗
PubMed1989

A prospective randomized trial of doxorubicin versus idarubicin in the treatment of advanced breast cancer.

Seventy-six patients with advanced breast cancer were entered into the current study. They were randomized to receive either idarubicin (IDA) 45 mg/m2 orally or doxorubicin (DX) 75 mg/m2 intravenously (IV), both drugs being administered every 3 weeks. Among 37 evaluable patients who received DX treatment the overall response rate was 46%, whereas it was 21% in 34 evaluable patients treated with IDA. This difference was statistically significant. In previously untreated patients the response rate with DX was 60% compared to 29% with IDA. Patients with prior chemotherapy had 29% response rate to DX in contrast to 12% with IDA. The median time to response, the median response duration, and the median time to progression were similar in both groups. The median survival of all patients was 20 months in DX arm and 14 months in IDA arm (95% confidence limits 16.69-23.31 and 10.77-17.23, respectively; P = 0.09). Both treatments produced equivalent incidence and severity of myelotoxicity. Gastrointestinal toxicity and alopecia were significantly lower in patients receiving IDA. As for cardiotoxicity, four cases of congestive heart failure were recorded among patients treated with DX whereas no cases occurred in the IDA group. The results of this study indicate that, although DX remains the best single agent available in the treatment of breast cancer, IDA may have a role in selected patients with this disease.

Adult↗
PubMed1989

Prognostic factors influencing cisplatin-induced emesis. Definition and validation of a predictive logistic model.

Data obtained from 209 patients who entered different prospective randomized antiemetic trials were analyzed to establish the prognostic value of some variables on the control of cisplatin-induced emesis. The antiemetic regimens evaluated included the following: metoclopramide (M) at 1, 2, and 4 mg/kg total dose and a combination of M (4 mg/kg) with dexamethasone (D) (40 mg). Vomiting lasting more than 1 hour (no protection [NP]) was the endpoint selected for the analysis. A logistic model carried out, first on the 110 subjects receiving the M + D regimen and then on the whole sample, selected sex (P = 0.0001), Eastern Cooperative Oncology Group performance status (PS) (P = 0.006), and age (P = 0.01) among the six factors considered. Since the prognostic value of these variables is mostly related to their interaction, three major risk classes were identified. The corresponding NP rates were 26.3%, 42.4%, and 70.8% for the low-risk, intermediate-risk, and high-risk groups, respectively (P = 0.000002). Except for the lowest M level, the observed NP rates were significantly associated to the risk classes, whereas the antiemetic regimen influenced the antiemetic outcome only in the low-risk class. Regardless of the regimen employed, certain patient characteristics, such as sex, PS, and age, significantly affect cisplatin-related emesis and should be carefully considered in planning further studies.

Adult↗
PubMed1989

Prognostic variables in recurrent limb melanoma treated with hyperthermic antiblastic perfusion.

Between October 1969 and December 1986, 136 patients with recurrent limb melanoma were treated with hyperthermic antiblastic perfusion (HAP). This retrospective analysis is aimed at identifying tumor-related and treatment-related variables likely to influence tumor response, locoregional control, disease-free survival, and overall survival. Independent factors predicting a complete response (CR) were the number of lesions (P less than 0.0001) and the minimum tumor temperature (minT) (P = 0.03). Only a positive trend was observed for the drug dose (P = 0.08). However, the proportion of CR was significantly higher (57.7%; P = 0.02) in patients who had a minT of 41.5 degrees C or greater and who were given a dose equal to or greater than the standard dose than in patients treated with lower temperatures and/or lower drug doses. The occurrence of a CR significantly increased the rates of locoregional control (77%; P = 0.007), disease-free survival (55.6%; P = 0.006), and overall survival (68.6%; P = 0.03). Treatment optimization may provide further therapeutic improvements by increasing the incidence of CR. However, the overall survival rates also were influenced by the number of lesions (P = 0.0014), sex (P = 0.04), and the number of previous relapses (P = 0.01). Therefore, tumor aggressiveness also is crucial in determining the outcome of the disease, and only early treatment with HAP can reduce the risk of distant metastases.

Adult↗
PubMed1989

Multivariate analysis of a tissue CEA, TPA, and CA 19.9 quantitative study in colorectal cancer patients. A preliminary finding.

Tissue CEA, TPA, and CA 19.9 concentrations from samples of surgical specimens were measured in 47 evaluable colorectal cancer patients (median follow-up, 20 months, 13 recurrences) and correlated with individual patient follow-up status. The quantitative method appeared to be sensitive, easily reproducible, and standardizable. The tissue marker concentration was analyzed by means of the multivariate discriminant analysis, to evaluate the risk of relapse in each patient; the tumor CEA (CEA T) showed the best discriminant capacity (P = .005). The relative Fisher function provided a reliable prognostic patient index, independently of other recognized prognostic factors (Dukes' stage and cellular differentiation grade). The Cox model showed a statistical significance analyzing the tumor (T) and healthy mucosa (M) CEA values (P = .001 and P = .006, respectively). The combination of these two variables allowed for identification of three classes of patients according to CEA T and M threshold values of 216 and 85 ng/mg of protein, respectively, and different disease-free curves were obtained for each group. The two-year disease-free rate was 81 percent for patients with low values of both CEA T and M, and 21.4 percent for the group with both values above these thresholds (P = .0008). In the third class (CEA T or M higher than the reported cut-off levels), the two-year disease-free rate was 65.9 percent.

Antigens, Neoplasm↗
PubMed1989

The responsiveness of bone metastases to radiotherapy: the effect of site, histology and radiation dose on pain relief.

281 patients with a total of 463 symptomatic osseous metastases treated for palliation between 1975 and 1985 have been retrospectively analysed. The most frequent primary sites were breast (50.1%) prostate (16.6%) and lung (11%), accounting for more than three fourths of all metastatic areas. Other primaries were represented by bladder, kidney, colorectal, uterus (corpus and cervix) melanoma and thyroid tumors, and by cancer from unknown origin. Palliation was evaluated only on a subjective pain score. Complete response meant complete pain relief, and partial response meant more than 50% and less than complete pain relief in all treated sites. Complete response rates were similar independently from the primary site, except for the adenocarcinomas of the kidney and for non-small cell carcinomas of the lung in which the response tended to be lower. A correlation was also found between the incidence of pain relief and the site of bone metastases, in that a lower response was shown in limb localizations. Also, the number of metastatic sites did not influence the complete response rate. As expected, the response rate in all cases seemed to be dependent on total absorbed dose while, surprisingly, it could not be shown to be affected by the fraction size. A similar trend was shown for the pain recurrence.

Adult↗
PubMed1989

Effective control of CMF-related emesis with high-dose dexamethasone: results of a double-blind crossover trial with metoclopramide and placebo.

To establish the antiemetic activity of both dexamethasone (DXM) and metoclopramide (MCP) in patients receiving i.v. cyclophosphamide, methotrexate, and 5-fluorouracil (CMF), 25 women with stage II breast cancer were entered into this study. A randomized, double-blind, crossover design was employed to evaluate DXM (24 mg in 5 doses) versus MCP (1 mg/kg as a single dose) versus a combination of both drugs (as above) or placebo (PLC). The patients were requested to complete a questionnaire evaluating the antiemetic effect. All but one patient completed the planned antiemetic program during the first four CMF courses. As compared to PLC, both the DXM-MCP combination and DXM alone provided a higher complete antiemetic protection rate (p = 0.01 and p = 0.006, respectively). The DXM regimens were more effective than both PLC (p = 0.004 and p = 0.01) and MCP (p = 0.002 and p = 0.006) in reducing the prevalence of severe vomiting. As compared to MCP, the DXM regimens provided a better control of the nausea (p less than 0.04 and p less than 0.01) and reduced both the episodes and the duration of vomiting (p less than 0.02 and p less than 0.05). The DXM regimens were also associated with a better patient opinion than the PLC (p less than 0.002 and p less than 0.0002). No significant differences were found between MCP and PLC, nor between the DXM regimens. Except for two dystonic reactions, MCP-related toxicity was mild, whereas that induced by DXM was negligible in patients with no contraindications to corticosteroids. As employed in this study, DXM provided safe and effective antiemetic protection for patients receiving adjuvant i.v. CMF. Data available do not support the use of a short-course MCP, either alone or in combination with DXM. The search for better antiemetic treatments is mandatory, especially for patients receiving adjuvant chemotherapy. To date, we recommend the use of DXM as a standard regimen and as a control for further studies.

Adult↗
PubMed1989

Prognostic factors for chemotherapy response and survival using combination chemotherapy as initial treatment of advanced head and neck squamous cell cancer.

Between May 1981 and December 1987, 152 consecutive patients with locally advanced and previously untreated head and neck squamous cell cancer (HNSCC) received two or three courses of neoadjuvant chemotherapy (NAC) prior to surgery and/or radiotherapy. Eighteen percent of patients achieved a complete response and 45% a partial response (PR), for an overall response rate of 63%. A variety of pretreatment patient and tumor characteristics were analyzed for both the tumor response to NAC and survival rate. Significantly higher CR rates were found in patients with a World Health Organization (WHO) performance status (PS) of 0 to 1 than in those patients with a PS of 2 (P = .03). Patients with stage III disease were significantly more likely to respond than those with stage IV (P = .006). Evaluation of all parameters through multivariate analysis identifies the tumor classification (P = .001) and the primary site (P = .006) as the most significant in predicting CR. The overall 5-year survival rate of the entire group of patients was 18% (median survival, 14.3 months). Analysis by PS (P = .001), stage (P = .002), and tumor (P = .001), and node (P = .01) classes showed significant differences. Patients achieving a CR after NAC had a significantly improved survival rate as compared with those with residual disease at assessment (P = .0003). With the multistep regression analysis, the tumor (P = .005) and node (P = .007) classifications, and the sex (P = .03) were significant factors, but CR (P = .0004) remained the most important and independent predictive factor. Randomized prospective trials are requested to clearly establish the role of NAC on survival rates.

Adult↗
PubMed1988

Neoadjuvant chemotherapy in previously untreated patients with advanced head and neck squamous cell cancer.

Between May 1981 and January 1986, 130 consecutive patients with advanced untreated head and neck squamous cell cancer (HNSCC) received neoadjuvant chemotherapy (NAC) with two or three courses of the CABO combination (methotrexate 40 mg/m2 intravenously (IV) on days 1 and 15; CDDP 50 mg/m2 IV on day 4; bleomycin 10 mg IV on days 1, 8, and 15; and vincristine 2 mg IV on days 1, 8, and 15 every 3 weeks) prior to surgery and/or radiotherapy. Of the 123 patients evaluable for response to chemotherapy, 19 (15.4%) had a complete remission and 59 (48%) a partial response, yielding a 63.4% overall response rate. Response rate was significantly correlated with the performance status (PS) (P = 0.001), the stage (P = 0.005), and the T class (P = 0.02); 107 patients completed subsequent local treatment (87 with radiotherapy and 20 with surgery +/- radiotherapy). The median survival of the 124 patients evaluable for survival was 14.7 months and the overall survival rate at 3 years was 24%. The median survival and the overall survival at 3 years for the surgical subgroup were 24.7 months and 38% and for the radiotherapy subgroup were 14.3 months and 22%. These results were compared with those obtained in a historical control group of 79 patients treated in our institute with short courses of chemotherapy regimens, which did not include cisplatin, followed by radiotherapy (29 patients) or local treatments alone (26 patients with radiotherapy and 24 patients with surgery +/- radiotherapy) between January 1976 and December 1980. Most of the patient characteristics were evenly distributed (age, sex, and primary sites) except that more advanced lesions were included in the NAC group (Stage IV: 85% versus 62%; T4: 65% versus 42%; N2-3: 48% versus 29%). The overall survival was significantly higher in patients receiving NAC than in the historical control group, comparing both the groups taken as a whole (P less than 0.05) and the surgery +/- radiotherapy (P less than 0.05) and the radiotherapy (P less than 0.02) subgroups. This experience suggests a positive role of NAC on survival. However, this improvement in outcome compared with a historical control group cannot be regarded as definitive evidence for benefit to patients. Randomized studies using active regimens are required to confirm these data.

Aged↗
PubMed1984

Acute leukaemia in patients treated for Hodgkin's disease.

Fourteen acute non-lymphoid leukaemias (ANLL) were identified among 947 consecutive patients with Hodgkin's disease (HD) treated in five collaborating centres in Italy between January 1969 and December 1979. Leukaemia developed 12-118 months after the diagnosis of HD and was always preceded by a pre-leukaemic phase. The karyotype of the leukaemic cells was studied in nine of the 14 patients and was abnormal in seven cases. Bone marrow agar cultures were performed in five of the 14 patients and were abnormal in every case. The actuarial risk of developing ANLL at 10 years was 6.2% for combined therapy, 4.8% for salvage therapy and 2.2% for chemotherapy alone. No case of ANLL was documented among 136 patients treated with radiotherapy alone. One patient developed acute promyelocytic leukaemia following treatment with ABVD and radiotherapy. Both univariate and multivariate analyses seem to demonstrate that the induction therapy modality is a significant variable in development of secondary acute leukaemia. The recognition of a significant risk of ANLL in patients treated for HD should create changes in treatment policy.

Actuarial Analysis↗
PubMedDate not supplied

The application of hyperthermia in regional chemotherapy.

To evaluate the role of hyperthermia combined with chemotherapy in the loco-regional treatment of tumors, a retrospective analysis was done with 228 limb melanoma patients treated with hyperthermic antiblastic perfusion (HAP). A series of treatment- and tumor-related prognostic factors was analyzed to establish their influence on tumor response, loco-regional control, and survival. Concerning tumor response, the logistic model showed that the number of lesions and the minimal tumor temperature (min T) maintained their individual predictive values (P < 0.000001 and P = 0.04, respectively). For loco-regional control, only the number of lesions had a significant predictive value. No direct correlation was found between the treatment-related variables and loco-regional control. However, the 5-year survival rate was significantly higher for patients who achieved a complete response (CR) (51.5%, P = 0.0033) as compared to those who did not (33.3%), providing indirect evidence of the role of the treatment. Multivariate analysis showed that both disease-free and overall survival are strongly influenced by numerous clinical variables and the min T always maintained its significance. When analyzing the subgroup of 119 patients evaluable for tumor response, the Cox model selected the tumor response as the dominant factor for both disease-free and overall survival. These data seem to demonstrate that the optimization of treatment parameters is crucial in determining the CR rate, which, in turn, positively affects the disease outcome. HAP is the treatment of choice for recurrent limb melanoma, and hyperthermia plays an important role in exploiting the efficacy of this technique.

Antineoplastic Agents, Alkylating↗
PubMedDate not supplied

Hyperthermic antiblastic perfusion in the treatment of local recurrence or "in-transit" metastases of limb melanoma.

On the basis of personal experience and a review of the literature, the authors have evaluated the results obtained with hyperthermic antiblastic perfusion (HAP) for the treatment of stage II, III and IIIAB limb melanoma. The evaluation showed that today HAP may be considered a safe and effective treatment, with a major complication rate ranging between 1% and 4%. In terms of tumor response, locoregional control and survival, this treatment has provided better results than other regional chemotherapeutic modalities and undoubtedly better results than those obtained with conventional, even radical, surgery. The multiparametric analysis showed that, of the treatment-related prognostic factors, the minimum tumor temperature influenced the percentage of complete response (CR) to the greatest extent (P < 0.03), with a positive trend also with regard to the dosage of the antiblastic drug employed (P < 0.08). In turn, the complete response rate was a determinant as far as locoregional control (75.3%; P < 0.0009) and disease-free (51.4%; P < 0.009) and overall survival (63.2%; P < 0.009) rates were concerned. Of the tumor-related prognostic factors, the number of lesions (P < 0.0014), sex (P < 0.04), and the number of disease recurrences (P < 0.01) appear to influence overall survival.

Chemotherapy, Cancer, Regional Perfusion↗
PubMedDate not supplied

N-methylformamide affects spontaneous metastases of 3LL lines and increases natural killer activity of tumor-bearing mice.

The antitumor activity of the polar solvent N-methylformamide (NMF) was evaluated on three lines derived from the Lewis lung carcinoma (3LL), endowed with different metastatic potential. Two administration schedules were tested, these being repeated regimens of NMF (200 mg/kg per dose) for 12 consecutive days, starting 24 h or 6-10 days after tumor implantation (early or late treatment, respectively). The results of the present work can be summarized as follows: (1) NMF regimens did not greatly affect tumor growth behavior of 3LL lines; conversely, they markedly influenced their spontaneous colonizing ability in the lungs, either by delaying early metastatic spread or by reducing the number and size of pulmonary metastases already implanted. (2) A significant increase of NK cell activity during and after early treatment with NMF was observed in the more-metastasizing lines, thus suggesting the possibility of an immunomodulating effect of NMF.

Animals↗
PubMedDate not supplied

Comparative analysis of CEA and SCC serum markers with IAP in human lung cancer.

Serum levels of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and immunosuppressive acidic protein (IAP) were measured in 37 patients with lung cancers, in 24 with non-cancer pulmonary diseases and in 24 normal controls We evaluated the sensitivity, specificity and accuracy of these three markers alone and combined. The highest specificity was observed for SCC (83.3%) and the highest sensitivity for IAP (94.6%). The best accuracy was obtained with the combined determination of CEA and SCC. In cancer and non-cancer pulmonary diseases the best correlation was observed between CEA and SCC (r = 0.30 in cancer and r = 0.45 in non-cancer pulmonary diseases). Although the IAP test is not specific in the detection of lung cancer, its use may be helpful in monitoring the acute phase reactions that occur very frequently in this malignancy.

Adenocarcinoma↗
PubMedDate not supplied

[Utility of endoscopic follow-up after resection of colorectal cancer].

PURPOSE: Patients resected for colorectal cancer are at increased risk for an anastomotic recurrence, for adenomatous polyps and for a metachronous cancer. A regular colonoscopic surveillance in these patients is justified for early detection and potential resection of anastomotic recurrences, new primary cancer and adenomatous polyps. PATIENTS AND METHODS: 322 patients were observed and resected for colorectal cancer between 1970 and 1988, with complete staging agreed to be included in a follow-up program (median follow-up: 105 months). To December 1993 all the patients were submitted to colonoscopy once yearly for the first 5 years and then every 2 years. RESULTS: Anastomotic recurrence was observed in 22 of the 253 patients who underwent resection for rectal or sigmoid adenocarcinoma (8.7%). Sixteen of these patients were submitted to a second curative resection with a median survival of 35 months; the median survival was 6 months in the 6 patients who could not undergo this operation (p = 0.0018). Metachronous adenomas of the residual colon were found in 24 patients (7.4%) and metachronous cancers in 5 (1.5%) at Stage A, according to Dukes' classification. CONCLUSIONS: In patients resected for rectal or sigmoid carcinoma, a sigmoidoscopy should be performed every 6 months for the first 2 years for the early detection of anastomotic recurrences. In all cases, a colonoscopy should be performed every 5 years after surgery to detect metachronous lesions at early stage. Before surgery, a "clean colon" should always be established to detect possible synchronous lesions.

Adenocarcinoma↗
PubMedDate not supplied

[Peritonectomy and chemohyperthermia in the treatment of peritoneal carcinomatosis: learning curve].

A prospective study has been carried on 37 patients affected by peritoneal carcinomatosis from various primary. Patients have been treated by cytoreductive surgery and intraoperative hyperthermic chemoperfusion. CC 0-1 has been achieved in 81%. The temperature distribution study showed a "barrier effect" with no statistically significant correlation to the survival. Major morbidity and mortality was respectively 37.8% and 16.2%. Two-yr overall survival was 49.1% for all series. Morbidity was significantly directly correlated to the duration of the surgical treatment. A learning curve of 19 months have been observed, after that only one death out 21 procedures has been recorded. Peritoneal carcinomatosis patients, that are submitted to integrated treatment, need a peculiar management that is not comparable to any other in the oncological setting and that requires specific competence.

Carcinoma↗