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Biomedical subjects

S Chiara

Publications and source records attributed to S Chiara.

At least 19 recordsLinked to original sources
PubMed2005

Capecitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentric phase II study.

BACKGROUND: The aim of the study was to evaluate tolerance and efficacy of preoperative treatment with capecitabine in combination with radiation therapy (RT) in patients with locally advanced, resectable, rectal cancer. PATIENTS AND METHODS: Fifty-three patients with potentially resectable T3, N0-2 (87%) and T4, N0-2 (13%) rectal cancer were treated with capecitabine (825 mg/m2, twice daily for 7 days/week) and concomitant RT (50.4 Gy/28 fractions). Patients underwent surgery after 6-8 weeks followed, upon physician's indications, by 4-months adjuvant capecitabine. The primary end point was to determine the rate of pathologic complete response. Secondary end points were to assess the rate of clinical response and the safety profile. RESULTS: All patients but two completed the RT programme and 47 (89%) received 81%-100% of the capecitabine dose (100% of dose in 72% patients, 81%-95% in 17% patients and 48%-74% in 11% of patients). No patient had grade 4 toxicity. Grade 3 toxicity occurred in six patients (11%) and consisted mainly of leucopenia (4%) and hand-foot syndrome (4%). Mild or moderate toxicity was common and included leucopenia (72%), diarrhea (40%), proctitis (34%) and skin toxicity (20%). The overall clinical response rate was 58% and the downstaging rate was 57%, with a pathologic complete response rate of 24%. Among 34 patients with low-lying tumors (<or=5 cm from anal verge), 20 (59%) had a sphincter-saving operation. CONCLUSIONS: Preoperative chemoradiation with capecitabine and RT appeared to be effective in locally advanced resectable, rectal cancer. The favorable safety profile of the combination might warrant the use of capecitabine and RT with other effective new drugs.

Administration, Oral↗
PubMed2001

Advanced ovarian cancer in the elderly: results of consecutive trials with cisplatin-based chemotherapy.

From 1982 through 1996, 547 untreated advanced ovarian cancer patients were entered onto Gruppo Oncologico Nord-Ovest (GONO) consecutive randomized trials including cisplatin-based chemotherapy. End points of analysis included the influence of age on prognosis, toxicity, clinical/surgical response rates, progression-free survival and survival. Of the entire study group, 116 patients were 65 years of age or older at diagnosis. WHO main toxicity (any grade) consisted of: emesis (93% of patients), myelotoxicity (leukopenia in 52%, anemia in 51% and thrombocytopenia in 17% of patients), nephrotoxicity in 13% of patients and neurotoxicity in 10% of patients. No significant difference in toxicity was evident between patients > or = or <65 years. Refusal of CT and early (< or =2 courses) interruption of CT due to toxicity were more frequent in elderly patients (3.4 vs. 1.4%; 3.4 vs. 0.7%, respectively). After a median follow-up of 71 months no difference was observed in survival and progression-free survival between younger and older patients. Cox multiple regression analysis of the entire study population demonstrated that age >65 years per se was not a negative prognostic factor.

Adult↗
PubMed2001

Gemcitabine in advanced pancreatic cancer: a phase II trial.

The 5-year survival for pancreatic cancer is usually less than 5%, and no treatment has demonstrated consistent effect on patient survival and disease-related symptoms. Early studies with gemcitabine suggested a modest antitumor activity with significant improvement in disease-related symptoms. This phase II study reports the activity of gemcitabine on 33 consecutive patients with unresectable pancreatic carcinoma. Twenty-three patients had metastatic and 10 locally advanced unresectable disease. Twenty-six patients had not received any previous treatment and seven had received first-line chemotherapy with 5-fluorouracil. Gemcitabine 1,000 mg/m2 was administered intravenously in 30 minutes in the first cycle once weekly for up to 7 weeks followed by 1 week rest; then in subsequent cycles, once weekly for 3 of every 4-week cycle. Four patients obtained partial response (12%). Fifteen patients (45%) had stable disease with a median duration of 32 weeks (range: 16-75 weeks), and 14 patients experienced progressive disease. Median duration of response was 34.5 weeks (range: 19-50 weeks). Median survival was 33 weeks (range: 2-91 weeks). All 4 responding patients and 14 of 15 (93%) patients with stable disease had improvement in performance status and decrease in daily analgesic requirement. Toxicity was mild and mainly consisted of moderate and rapidly reversible myelosuppression. We conclude that gemcitabine chemotherapy was very well tolerated and determined a significant clinical improvement with modest antitumoral activity in patients with advanced pancreatic cancer.

Aged↗
PubMed2000

Intraperitoneal versus intravenous cisplatin in combination with intravenous cyclophosphamide and epidoxorubicin in optimally cytoreduced advanced epithelial ovarian cancer: a randomized trial of the Gruppo Oncologico Nord-Ovest.

Intraperitoneal chemotherapy has a strong biological and pharmacological rationale in the treatment of ovarian cancer. From 1989 to 1996 the present study included 113 patients with FIGO stage II-IV ovarian cancer with residual disease less than 2 cm who were randomly allocated to receive 50 mg/m(2) intraperitoneal cisplatin (CDDP) plus 60 mg/m(2) intravenous epidoxorubicin (EPIDOX) and 600 mg/m(2) intravenous cyclophosphamide (CTX) (ipPEC arm) or 50 mg/m(2) intravenous CDDP plus 60 mg/m(2) intravenous EPIDOX and 600 mg/m(2) intravenous CTX (ivPEC arm). Chemotherapy was repeated every 4 weeks for six cycles. Treatment protocol was changed in 22 patients, 2 from the iv arm (who received single-agent carboplatin) and 20 from the ip arm (who were crossed to systemic chemotherapy, ivPEC, or single-agent carboplatin). At the end of chemotherapy, a second-look was performed in 33 of the 54 patients from the ip arm and in 34 of the 57 patients from the systemic arm. The pathologic complete response rate was 41% of all entered patients and 69% of patients submitted to second-look. No significant difference in pathologic response rate as well as in hematologic and nonhematologic toxicities was seen between the two arms. Up to September 1998, 72 patients showed a disease recurrence (33 treated with ipPEC and 39 treated with ivPEC), 55 died (22 ipPEC and 30 ivPEC), and 10 were lost to follow-up (6 ipPEC and 4 ivPEC). Median progression-free survival was 42 and 25 months for ipPEC and ivPEC, respectively (p = 0.13). Median overall survival was 67 and 51 months for ipPEC and ivPEC, respectively (p = 0.14). In conclusion, besides confirming that intraperitoneal chemotherapy is feasible with acceptable toxicity but with poor compliance in community hospitals, this trial showed that intraperitoneal CDDP compared with intravenous CDDP in combination with EPIDOX and CTX obtained a slight (not significant) improvement in progression-free survival and overall survival of optimally cytoreduced advanced ovarian cancer patients.

Adult↗
PubMed1998

Advanced colorectal cancer in the elderly: results of consecutive trials with 5-fluorouracil-based chemotherapy.

To evaluate toxicity and efficacy of chemotherapy in elderly patients (> or = 65 years of age) with advanced colorectal cancer, data from two consecutive trials conducted between 1984 and 1995 at the National Institute for Cancer Research were analysed comparing the results of treatment in those 65 years of age or older and in those younger than 65 years. Of 215 patients recruited, 82 elderly patients (median age 70 years, median performance status 1) received one of the following regimens based on 5-fluorouracil (5-FU): (1) weekly 5-FU 600 mg/m2 i.v. bolus (30 patients); (2) weekly 5-FU 600 mg/m bolus plus leucovorin (LV) 500 mg/m2 2-h i.v. infusion (28 patients); (3) Weekly 5-FU 2600 mg/m2 24-h continuous i.v. infusion plus LV 100 mg 4-h i.v. infusion and 50 mg orally every 4 h for five doses (24 patients). Overall, 1071 chemotherapy cycles were administered with a median number of 12 courses per patient. The main side effects were diarrhoea, observed in 38% of patients, stomatitis in 24% of patients and hand-foot syndrome in 13% of patients, and haematological toxicity affected only 15% of patients. No patient suffered grade IV toxicity. In three patients chemotherapy was discontinued because of toxicity (two patients suffered grade III diarrhoea, one patient grade III hand-foot syndrome). No significant difference in toxicity was evident between patients older than or younger than 65 years. Analysis of median dose intensity demonstrated no difference between the two groups. Overall objective response was observed in 18% (95% confidence limits 11-29) of elderly patients (15/82) in comparison with 23% (95% CL 17-32) of patients < 65 years of age (31/133 pts). In conclusion, chemotherapy in elderly patients with advanced colorectal cancer is a safe and effective treatment with acceptable toxicity and comparable objective response rates.

Administration, Oral↗
PubMed1997

Hand-foot syndrome induced by high-dose, short-term, continuous 5-fluorouracil infusion.

The aim of this study was to examine in detail the incidence and severity of hand-foot syndrome in advanced colorectal cancer patients receiving 5-fluorouracil (5-FU) and leucovorin (L-LV) chemotherapy. 70 advanced colorectal cancer patients (pts) were given weekly 24 h continuous 5-FU (2600 mg/m2) infusion plus L-LV (100 mg/m2 i.v., 50 mg orally). The toxicity, in particular HFS, was analysed, correlated to the main pts characteristics and compared to the other observed side-effects. HFS occurred in 36/70 pts (51%): grade 1 in 16 pts, grade 2 in 16 pts, grade 3 in 3 pts and grade 4 in 1 pt. It occurred after a median number of nine courses. In one case, chemotherapy was interrupted for this toxicity, and in another 5 pts drug reduction and/or treatment delay were undertaken. Changes in the therapeutic programme because of diarrhoea or mucositis were more frequent, even though these toxicities were generally mild in our series of pts. HFS was significantly correlated to previous exposure to chemotherapy (P = 0.00003). HFS was a frequent side-effect of high-dose, short-term continuous 5-FU infusion, but the impact on quality of life of pts and on the correct delivery of the planned chemotherapy was limited.

Adult↗
PubMed1996

High-dose versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin in suboptimal ovarian cancer: a randomized study of the Gruppo Oncologico Nord-Ovest.

PURPOSE: The aim of the study was to compare high-versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin as primary chemotherapy for suboptimal stage III and IV ovarian cancer. PATIENTS AND METHODS: One hundred forty-five patients were randomized to receive six courses of cisplatin 50 or 100 mg/m2 plus epidoxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2. The two treatment arms were well balanced; all patients had greater than 2 cm and 37.2% had greater than 5 cm of residual disease; 29.6% had stage IV disease. RESULTS: Patients in the high-dose arm received a double dose-intensity and double total dose of cisplatin. The high-dose regimen induced significantly more episodes of leukopenia (47.8% v 32.8%, P = .05), thrombocytopenia (21.7% v 3.2%, P = .003), anemia (37.6% v 12.5%, P = .002), nephrotoxicity (six v one patient), and neurotoxicity (30.4% v 6.3%, P = .002). There were no significant differences in efficacy in terms of clinical response rate (high-dose 57.5% v low-dose 61.1%), pathologic complete response (CR) (9.6% v 18.1%), median survival times (29 v 24 months), and median progression-free survival (18 v 13 months). CONCLUSION: This study shows that doubling the dose-intensity and total dose of cisplatin in combination with epidoxorubicin and cyclophosphamide has significant toxic effects and does not improve clinical outcome in patients with suboptimal ovarian cancer.

Adult↗
PubMed1995

Long-term prognosis following macroscopic complete response at second-look laparotomy in advanced ovarian cancer patients treated with platinum-based chemotherapy. The Gruppo Oncologico Nord Ovest.

Survival (S) and progression-free survival (PFS) were evaluated in 129 advanced ovarian cancer patients, who achieved a macroscopic complete response (112 pathological complete response and 17 microscopic disease) at second-look after platinum-based combination chemotherapy with or without doxorubicin (DX). The impact on S and PFS of age, performance status (PS), stage, histology, grade (G), residual disease after first surgery (RD), chemotherapy regimen, disease status at second-look and consolidation therapy were evaluated by univariate and multivariate analysis. In the 118 months observation period, median S and PFS were 81 and 34 months, respectively. Stage, G, RD, PS and disease status at second-look had significant impact on both S and PFS in univariate analysis, whereas consolidation therapy did not influence outcome. Cox's regression analysis showed that G, RD and PS had an independent impact on PFS. Test for interaction demonstrated no statistically significant relationship between RD, chemotherapy regimen and outcome. In conclusion, advanced ovarian cancer patients with macroscopically complete remission at second-look have a substantial risk of relapse after aggressive treatment. The risk of recurrence was estimated to be maximal in the first 3 years after restaging, and was correlated with poor PS, RD > 2 cm after first surgery and undifferentiated tumour.

Adult↗
PubMed1994

Tumour kinetics, response to chemotherapy and survival in primary ovarian cancer.

The analysis of thymidine labelling index (TLI) in relation to clinico-pathological variables and survival was carried out in 111 ovarian cancer patients. The significance of TLI in predicting response to aggressive first line chemotherapy regimens was examined. The overall median TLI value of 1.8% was used as a cut-off to discriminate slowly from highly proliferating cancers. 94 patients entered into two consecutive randomised trials, and were treated with six courses of cisplatin-based chemotherapy with or without doxorubicin. A significantly higher objective response of 60% was reported in the subset of patients with TLI > 1.8% as compared to 35% in patients with TLI < or = 1.8% (P = 0.03). In addition, patients achieving complete response had tumours with median TLI of 3.8% as compared to 2.4% for partial responders, 1.5% for patients with stable disease and 1.7% for those with progressive disease. A significant increase in tumour kinetics was observed in advanced cancers (P = 0.001), more undifferentiated tumours (P = 0.02) and postsurgical residual disease greater than 2 cm (P = 0.04). In univariate analysis, TLI failed to influence significantly clinical outcome: 26 versus 32 months median survival time for patients with high and low tumour TLI, respectively. In the Cox's regression model, the only independent prognostic variables were performance status and amount of residual disease after primary surgery (P = 0.000).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

High-risk early-stage ovarian cancer. Randomized clinical trial comparing cisplatin plus cyclophosphamide versus whole abdominal radiotherapy.

From 1985 to 1989 70 patients with high-risk FIGO Stage I-II ovarian carcinoma entered a randomized trial comparing chemotherapy (CT: cisplatin 50 mg/m2 + cyclophosphamide 600 mg/m2 day 1 every 28 days for 6 courses) versus whole abdominal radiotherapy (WAR) given according to the open-field technique (43.2 Gy/24 fractions to the pelvis and 30.2 Gy to the upper abdomen). Protocol violations occurred in 8 patients randomized to WAR who received CT because of their own and/or physician's decision. Since protocol compliance was poor and accrual low the study was prematurely closed. Treatment-related toxicity for patients receiving CT was mild and tolerable, consisting chiefly of controllable grade 3 emesis (71%). Grade 3-4 diarrhea was experienced by 28% of patients treated with WAR; severe enteritis requiring hospitalization was observed in 2 patients. Late bowel obstruction requiring surgery was observed in 1 patient. At a median follow-up of 60 months, 21 patients died and 23 relapsed. Five-year survival was 71% and 53% (p = .16), while relapse-free survival was 74% and 50% (p = .07) for CT and WAR, respectively. Although no firm conclusion can be drawn from the present study, a short-term CT, including cisplatin, appears a safe treatment in comparison to WAR.

Abdomen↗
PubMed1994

Randomized study comparing chemotherapy plus radiotherapy versus radiotherapy alone in FIGO stage IIB-III cervical carcinoma. GONO (North-West Oncologic Cooperative Group).

Between January 1989 and December 1991, 64 patients with advanced cervical carcinoma FIGO stage IIb-III were randomized to receive radiotherapy (RT) alone or the sequential combination of chemotherapy (CT) and RT. RT consisted of external RT (40 Gy fractionated over 4 weeks)+brachy-therapy (40 Gy to point A)+an additional boost to the parameters (15-20 Gy) in arm RT; CT consisted of cisplatin 60 mg/m2 i.v. day 1 q 15 days administered for 2 cycles before the start of RT and for 4 cycles after the end of radiation treatment in CT+RT arm. Among the 58 evaluable patients objective response rate was as follows: in RT arm, CR in 40.7% of patients, PR in 40.7%, and SD in 18.6%; in CT+RT arm, CR in 42% of patients, PR in 35.5%, and SD in 22.5%. The median duration of response was 12 months (range: 3-38 + months). At a median follow-up of 36 months survival (S) and progression-free survival (PFS) were 83% and 72.4% in RT arm, 72% and 59.3% in CT+RT arm, respectively. No significant difference was observed between the 2 treatment arms, neither in terms of objective response nor in terms of S and PFS. Both treatments were generally well tolerated. In our experience the addition of chemotherapy to standard radiotherapy does not enhance morbidity and does not interfere with the correct delivery of the planned treatment. However, results of this combined modality regimen remain unsatisfactory, since no improvement in pelvic control and survival of patients with advanced cervical carcinoma was observed.

Adult↗
PubMed1993

Cerebral metastases secondary to ovarian cancer: still an unusual event.

An incidence of cerebral metastases secondary to epithelial ovarian cancer as high as 11.6% has been reported in small series and related to the prolonged survival of ovarian cancer patients treated with platinum compounds (Hardy, J. R., and Harvey, V. J. Gynecol. Oncol. 33, 296-300, 1989). A review of the histories of 413 ovarian cancer patients, treated from 1981 to 1989 with platinum-based combination chemotherapy according to the protocols of the Gruppo Oncologico Nord Ovest (GONO) (North West Oncology Group), showed that only 9 patients (2.2%) developed clinical evidence of cerebral metastases. Six of 9 patients had FIGO Stage IIIc disease and 1 each with FIGO Stages Ic, IIc, and IV. All these patients had received cisplatin or carboplatin-based combination chemotherapy. Clinical response to initial cytotoxic therapy was as follows: complete response, 3 patients; partial response, 4 patients; stable disease, 1 patient; progressive disease, 1 patient. Cerebral metastases occurred at a median of 19 months (range 3-36) from diagnosis and median survival of patients with central nervous system (CNS) metastasis was 26 months (range 10-81) from diagnosis of primary disease and 8 months (range 1-45) from diagnosis of CNS involvement. The incidence of CNS metastases in our series is similar to that reported in the past and significantly lower than figures reported by the above mentioned paper. On the basis of our data we do not agree with Hardy and Harvey about the relationship possibly existing between prolonged survival and incidence of CNS metastases and, particularly, about the need for prophylactic cranial irradiation.

Aged↗
PubMed1993

The impact of received dose intensity on the outcome of advanced ovarian cancer.

It has been demonstrated that the prognosis of ovarian cancer is influenced by the dose intensity of cytotoxic treatment. The impact of received dose intensity of platinum-based combination chemotherapy on disease outcome was analysed in 226 stage III-IV ovarian cancer patients entered into two prospective randomised trials. All patients received either cisplatin or carboplatin and cyclophosphamide with or without doxorubicin for six courses after primary surgery. The impact of the received dose intensity of each drug (RDI), the average received dose intensity of the treatment regimen (ARDI) and the relative total drug dose (RTD) on progression-free survival (PFS) and survival were analysed. In the 198 patients receiving the full six courses of treatment, RDI of cisplatin or carboplatin, ARDI and RTD were > 0.76 in 74.2, 61.1 and 65.1% of cases, respectively. Although the differences were not significant, pathological complete response was more frequently observed in the group of patients with ARDI < 0.75, whereas the partial response rate was higher in the ARDI > or = 0.76 group. Median survival and PFS were 19 and 13 months; 22 and 10 months; 23 and 13 months for the groups of patients receiving chemotherapy at a ARDI of < 0.75, > or = 0.76-0.99 and > 1.00, respectively (P = not significant). It appears that modest dose modifications and brief treatment delays during first-line platinum-based chemotherapy do not affect response rate, survival and PFS in advanced ovarian cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Cisplatin-based chemotherapy in recurrent or high risk ovarian granulosa-cell tumor patients.

Nine chemotherapy-naive women with recurrent (2 patients) or high risk factors (bilateral or extraovarian spread, poorly-differentiated tumor, age > or = 40 years at diagnosis, residual disease after surgery) granulosa-cell tumors were treated with cisplatin, cyclophosphamide with or without doxorubicin (PAC, PC) or cisplatin, etoposide and bleamycin (PVP-16B). Toxicity was acceptable and the most frequently encountered adverse reactions were WHO grade 3 gastrointestinal toxicity in 77% of patients, and grade 3 myelosuppression in 22% of cases. Clinical complete response was achieved in the 2 patients with recurrent disease. Five patients underwent second look surgery which documented: complete response in 3 patients, partial response in 1 patient and progressive disease in 1 case. Median survival was 85 months (range 14-103). Cisplatin-based cytotoxic regimens may be of benefit in the treatment of recurrent or high risk granulosa-cell tumors.

Adult↗
PubMed1992

Prediction of survival by thymidine labelling index in patients with resistant ovarian carcinoma.

The relationship between tumour proliferative activity, evaluated by thymidine labelling index (TLI), clinicopathological variables and clinical outcome, was analysed in a series of 64 chemotherapy-resistant, ovarian cancer patients. The median TLI of 4.6% (range 0.01-45.7) was used as the cut-off to discriminate rapidly from slowly proliferating tumours. Univariate analyses showed a significant advantage in survival for patients with TLI less than or equal to 4.6 (P = 0.0004), ECOG performance status less than or equal to 1 (P = 0.0001) and residual disease after primary surgery less than or equal to 2 cm (P = 0.019). Multivariate analysis demonstrated that performance status was the only independent prognostic variable, although TLI was the last covariate removed from the Cox's regression model.

Carcinoma↗