Biomedical subjects

P Carlini

Publications and source records attributed to P Carlini.

49 records · Page 3Linked to original sources

PubMed1990

Primary hypothyroidism associated with interleukin-2 and interferon alpha-2 therapy of melanoma and renal carcinoma.

Four patients out of twenty with renal cancer and melanoma undergoing cancer immunotherapy with interleukin 2 (IL-2) and interferon alpha-2 (IFN-alpha 2) had laboratory evidence of hypothyroidism starting at cycle three to six, with a decline in serum thyroxine below normal and, in three cases, a rise in serum thyrotropin and thyroglobulin. One hypothyroid patient had elevated serum antimicrosomal antibody titres before the start of treatment and two others responded similarly during therapy. Three of the sixteen euthyroid patients also developed elevated titres of this antibody. Partial or complete remission was observed in seven of the patients--three of the four with hypothyroidism showed tumour regression. Thus IL-2 and IFN-alpha 2 can cause hypothyroidism, presumably via induction or exacerbation of autoimmune thyroid reactions. The occurrence of hypothyroidism may be mediated by high-dose IL-2 (rather than by LAK cell therapy as previously suggested) and potentiated by IFN-alpha 2.

Adult↗

PubMed1990

Dose and schedule effects of cisplatin on the related acute iron changes.

To investigate the relationships between cisplatin and the related erythropoiesis impairment, 14 patients receiving very-high-dose cisplatin (40 mg/m2/day for 5 days) and 17 patients receiving standard-high-dose cisplatin (either a single dose of 100 or 20 mg/m2/day for 5 days) entered this study. Iron, ferritin, hemoglobin, and reticulocyte levels were evaluated before, 4 and 6 days after each course of cisplatin. A complete blood count was obtained weekly. During the 1st week after chemotherapy, iron and ferritin levels significantly increased, and the reticulocyte count decreased. Iron changes depend on the cisplatin dose, but are not related to the different schedules employed. The severity of subacute anemia was found to be dependent on the cisplatin dose administered and on hemoglobin pretreatment levels. Some relationships between cisplatin, iron changes, and the subacute hemoglobin decrease are described.

Adult↗

PubMed1989

Fluctuations of plasma beta 2-microglobulin, soluble interleukin 2 receptor and interferon-gamma concentrations after adoptive immunotherapy with high-dose interleukin 2 and lymphokine-activated killer cells.

We report the serum levels of soluble interleukin 2 receptor (sIL2R), beta 2-microglobulin (beta 2-M) and interferon-gamma (IFN-gamma) in patients undergoing adoptive immunotherapy with rIL2 and lymphocyte-activated killer (LAK) cells. Our results indicate that rIL2 induced a marked increase of the serum concentration of these markers, although this increase varied considerably for different individuals. Parallel studies with the same patients also showed a marked rise in the number of IL2R+ lymphocytes: the IL2Rs expressed on these cells were mainly of the "low affinity" type. We suggest that evaluation of these markers may allow the monitoring of immune system activation induced by rIL2 in patients undergoing adoptive rIL2 and LAK cell immunotherapy.

Humans↗

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↗

PubMed1987

A randomized trial comparing alizapride alone or with dexamethasone vs a metoclopramide-dexamethasone combination for emesis induced by moderate-dose cisplatin.

To evaluate the antiemetic effectiveness and toxicity of a novel congener of metoclopramide (MCP), alizapride (AZP), 29 patients receiving cisplatin (50 mg/m2) alone or with adriamycin (40 mg/m2) were entered into a randomized cross-over trial comparing moderate-dose AZP (2 mg/kg for 4 doses) administered alone or with dexamethasone (DXM) (8 mg for five doses) vs a standard combination of MCP (1 mg/kg for four doses) and DXM (as above). With the dosage and schedule used, AZP provided only limited antiemetic protection, with less than 10% of the patients free of emesis. The AZP-DXM combination was significantly more effective than AZP alone in reducing the intensity of the emesis (P less than 0.03). The incidence, however, was statistically unaffected. The additional toxicity of DXM was negligible. Except for the patients' preference for MCP-DXM (P less than 0.01), no differences could be found between the DXM-based regimens, although a trend towards a better antiemetic effect with the MCP combination was evident. The benzamide-related dystonic reactions were equally distributed. Among the 11 patients affected there were 6 who required specific treatments. Unfavourable prognostic factors in the patient population could provide a reasonable explanation for the disappointing antiemetic protection obtained with all the regimens evaluated in this study.

Adult↗

PubMed1987

Alternating regimens in recurrent and metastatic squamous cell carcinoma of the head and neck.

In the present pilot study, two courses of CF and CABO combination chemotherapy were administered in an alternating manner to 27 patients affected with recurrent and metastatic squamous cell carcinoma of the head and neck. Of the 23 evaluable patients, 5 complete responses and 5 partial responses were observed; the overall response rate was 43.5%. Two out of five complete responders are still free of disease 30 and 65 weeks after the administration of CR. The toxicity of this program was tolerable and was carried out on an out-patient basis in all cases. The median survival of the entire group was 41 weeks (range 8-98.+). We conclude that these alternating regimens are not likely to produce better responses than other conventional cisplatin-including combinations, but they seem to significantly increase the duration of the response.

Antineoplastic Agents↗

PubMed1986

Cumulative or delayed nephrotoxicity after cisplatin (DDP) treatment.

The present retrospective study reports data regarding renal toxicity in 115 patients (63 males, 52 females; median age, 56 years) who received cumulative doses of cisplatin (DDP) greater than or equal to 200 mg/m2. DDP was administered alone or in combination at a dose of 50-70 mg/m2 in 91 patients, and at a dose of 100 mg/m2 in 22 patients. Two patients after progression of ovarian carcinoma treated with conventional doses of DDP received 4 and 2 courses, respectively, of high-dose DDP (40 mg/m2 for 5 days) in hypertonic saline. The median number of DDP courses was 6 (range 2-14), and the median cumulative dose was 350 mg/m2 (range, 200-1200). Serum creatinine and urea nitrogen were determined before initiating the treatment and again 13-16 days after each administration. The incidence of azotemia (creatinina levels that exceeded 1.5 mg/dl) was similar before (7.8%) and after (6.1%) DDP doses of 200 mg/m2. Azotemia appears to be related to the association of DDP with other potentially nephrotoxic antineoplastic drugs (methotrexate) more than to the dose per course of DDP. Of 59 patients followed for 2 months or more after discontinuing the DDP treatment, 3 (5.1%) presented creatinine values higher than 1.5 mg/dl. The data deny that the incidence of nephrotoxicity is higher in patients receiving higher cumulative doses of DDP and confirm that increases in serum creatinine levels may occur some time after discontinuation of the drug.

Adolescent↗

PubMed1986

Maintenance of antiemetic effect of a metoclopramide-dexamethasone combination during subsequent cisplatin courses.

In two previous consecutive studies on antiemetic combination of metoclopramide and dexamethasone was found to be very active against nausea and vomiting induced by cisplatin (DDP; 50 mg/m2) alone or in combination with other cytotoxic emetogenic drugs. In the present study the activity of the same antiemetic combination has been followed in 18 patients during subsequent DDP courses. Twelve out of 18 patients (67%) had a complete control of the side effect after the first course of chemotherapy. No statistically significant differences were found as regards the intensity of nausea and vomiting, the patients' overall opinions and preference and the emesis duration. In conclusion this antiemetic combination can guarantee a high degree and long-term control of DDP-induced emesis at a dose of 50 mg/m2 given alone or in combination.

Adult↗

PubMed1984

Improved control of cisplatin-induced emesis with a metoclopramide-dexamethasone combination.

Twenty-four patients receiving combination chemotherapy including cisplatin at a dosage of 50 mg/m2 were entered on this antiemetic randomized open cross-over study. High-dose dexamethasone (DXM) (regimen A) was compared with the combination of DXM and high doses of metoclopramide (MCP) (regimen B). Five patients (20%) treated with regimen A and 13 (54%) treated with regimen B suffered neither nausea nor vomiting (P less than 0.05). Regimen B was found to be significantly more effective than regimen A for all the parameters of evaluation considered. No severe side-effects were observed.

Adult↗

PubMed1984

Randomized open cross-over trial between metoclopramide (MCP) and dexamethazone (DXM) for the prevention of cisplatin-induced nausea and vomiting.

Thirty-five patients receiving chemotherapeutic regimens including cisplatin (CDDP) were entered into a randomized open cross-over trial. Sixteen patients had previously received chemotherapy. Metoclopramide (MCP) was given i.v. in 4 doses of 1 mg/kg over a period of 4 1/2 hr, dexamethazone (DXM) was administered i.m. in 4 doses of 8 mg over 24 hr and another 10 mg i.v. just prior to CDDP administration. Sixteen patients who expressed a positive opinion on both previous antiemetics were given placebo (PLC). No significant differences were found between MCP and DXM, considering the mean score of both emesis intensity and patient's opinion. The mean duration of the symptoms was significantly longer with MCP than with DXM (P less than 0.02). Both antiemetic agents were more effective than PLC. No significant side-effects were observed. The results of this study indicate that both MCP and DXM provide a similar protection against CDDP-induced nausea and vomiting.

Adult↗

PubMedDate not supplied

Efficient photosensitization of malignant human cells in vitro by liposome-bound porphyrins.

Comparative kinetics of porphyrin uptake and release by HeLa cells, incubated with equivalent concentrations of either hematoporphyrin (Hp) in aqueous solution or Hp and its dimethylester (HpDME) bound to unilamellar liposomes, show that liposomal porphyrins are bound at a higher rate and in considerably larger amounts. Moreover, the release of cell-bound porphyrins into the medium is remarkably reduced and slowered after cell loading with liposome-bound porphyrins. The presence of 1% bovine or human serum albumin (but not serum globulins) in the medium has no effect on uptake and release of liposome-bound porphyrins by HeLa cells, whereas it remarkably decreases the uptake of aqueous Hp. Parallel studies of cell photodamages under known concentrations of cell-bound porphyrin unequivocally demonstrate that the photodynamic effect is strictly related to the porphyrin load. As a consequence a dramatic increase of cell-photosensitizing efficiency is obtained by binding Hp (and even more HpDME) with liposomes. Electron microscopy investigations on cell damages caused by loading with liposome-bound porphyrins and subsequent illumination show that the plasmatic membrane is one important cell site of porphyrin interaction and photodynamic effect.

Cell Membrane↗

PubMedDate not supplied

Dramatic regression of multiple brain metastases from breast cancer with Capecitabine: another arrow at the bow?

Several chemotherapic agents, which are active against breast cancer, penetrate poorly into the central nervous system. Despite its limited brain penetration, 5-fluorouracil has been a component of effective regimens for brain metastases. Capecitabine is a recently developed oral prodrug that is converted into 5-fluorouracil by sequential enzymatic steps. Thymidine phosphorylase (TP) is the final enzyme responsible for Capecitabine activation. Studies have demonstrated that high intratumoral levels of TP and low levels of its catabolite dihydropyrimidine-dehydrogenase are correlated with the capecitabine response. The penetration of Capecitabine across the brain-blood barrier remains unknown; we report the case of and discuss a breast cancer patient who had an interesting response of brain metastases with Capecitabine in monochemotherapy before brain irradiation.

Adult↗