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Biomedical subjects

A Veronesi

Publications and source records attributed to A Veronesi.

At least 73 records · Page 4Linked to original sources

Presurgery chemotherapy (CT) in locally advanced bladder carcinoma: a feasible and possibly effective approach.

In October 1984, a prospective pilot study aiming to evaluate the feasibility and to preliminarily test the efficacy of the chemotherapy--surgery sequence in locally advanced bladder carcinoma was started at our institutions. Chemotherapy consisted of adriamycin 50 mg mq-2 and cisplatin 50 mg mq-2 on day 1 and fluorouracil 500 mg mq-2 and teniposide 100 mg mq-2 on days 1 and 8; chemotherapy was repeated every 3 weeks for three cycles and followed by surgery (radical cystectomy; TUR if radical surgery medically contraindicated). The characteristics of the 28 patients so far treated include: T3b in 26 patients, local relapse after surgery in two, nodal metastases in seven. Twenty-five patients were male and three female, median age was 61 yr (range 42-75). Clinical response following chemotherapy was: complete remission (CR) in five patients, partial remission (PR) in 15, stable disease (SD) in three, progression (PRO) in two. Three patients are not evaluable. Treatment was moderately well tolerated. Thirteen patients underwent radical surgery, three exploratory surgery, three TUR; refusal in three patients, early death in two, too early in one. No evidence of disease was found in the surgical specimen of five patients (three CR, two PR), microscopic residual disease in four PR patients, gross residual disease in 11 patients (one CR, six PR, two SD, two PRO). Actuarial median survival (all 28 patients) is 45% at 36 months. These preliminary results suggest that the combination of chemotherapy and surgery is feasible and may be effective in these poor prognosis patients.

Adult↗

Chemotherapy of advanced head and neck squamous carcinoma with cisplatin, fluorouracil and bleomycin administered in an outpatient schedule.

From May 1983 to September 1984, 48 consecutive patients with locally advanced, recurrent and/or metastatic head and neck squamous carcinoma were treated with cisplatin 60 mg/m2 i.v. on day 1, fluorouracil 10 mg/kg i.v. push from day 1 to day 4 and bleomycin 10 mg/m2 i.v. from day 1 to day 4, every 3 weeks. In the 44 evaluable patients complete remission was observed in 4, partial remission in 9, stable disease in 19, and progression in 12, for a 29.5% response rate. When the analysis was limited to the 21 patients with PS greater than 70 and no previous chemotherapy or radiotherapy, the response rate was 48%. Toxicity was acceptable, and no treatment related deaths occurred. Overall median survival (all eligible patients) was 7 months. Although further studies with this combination in poor risk patients (previously treated or with PS less than 70) do not appear to be indicated, a more accurate assessment in good risk patients might be warranted.

Adult↗

Chemotherapy of advanced non-small-cell lung cancer with cyclophosphamide, adriamycin, methotrexate, and procarbazine versus cisplatin and etoposide. A randomized study.

All consecutive eligible patients with non-small-lung carcinoma seen at Centro di Riferimento Oncologico and Istituto Nazionale per la Ricerca sul Cancro were entered into a randomized chemotherapy study. Conditions of eligibility included advanced stage (stage III not amenable to radiation therapy or i.v.), measurable or evaluable lesions, age less than 70 years, performance status (PS) greater than 40, and no previous chemotherapy. Patients were randomized to either CAMP (cyclophosphamide 300 mg/m2 i.v., adriamycin 20 mg/m2 i.v., methotrexate 15 mg/m2 i.v. days 1 and 8, procarbazine 100 mg/m2 orally from day 1 to day 10, every 4 weeks) or DE (cisplatin 20 mg/m2 i.v. for five consecutive days and etoposide 75 mg/m2 i.v. on the same days, every 3 weeks). Treatment was continued until progression. Out of the 136 patients randomized, 133 were eligible (CAMP 62, DE 71) and 108 evaluable. Patient characteristics included male/female ratio 57/5 (CAMP) and 61/10 (DE), median age of 60 years (CAMP) and 59 years (DE), PS greater than or equal to 70 for 39 (CAMP) and 50 (DE), PS less than 70 for 23 (CAMP) and 21 (DE), stage III for 18 (CAMP) and 15 (DE), and stage IV for 44 (CAMP) and 56 (DE). DE was superior to CAMP in terms of response rate, defined as responding/evaluable patient ratio (38.2% versus 20.8%); however, the responding/eligible patient ratio was not significantly different in the two groups. The superiority of DE tended to be more marked in stage III patients, in patients with PS greater than or equal to 70, and in the squamous histological type. Toxicity was acceptable (one toxic death) and evenly distributed in the two treatment groups; only renal toxicity was prevalent in the DE group. Survival (all eligible patients) was significantly better in the DE than in the CAMP group. Whether DE chemotherapy is superior to a no-chemotherapy approach has not been evaluated in this study and remains to be determined.

Antineoplastic Combined Chemotherapy Protocols↗

Cisplatin and etoposide as second-line chemotherapy in patients with small cell lung cancer.

Twenty-seven evaluable patients with small cell lung cancer (SCLC) resistant to, or relapsed after induction combination chemotherapy (CT) were treated with etoposide (VP16) plus cisplatin (DDP). Previous treatment was: alternating CT with cyclophosphamide (C), adriamycin (A), methotrexate (M), procarbazine (P) (CAMP)/VP16, BCNU (B), hexamethylmelamine (H) (VP16 BH) in 16 patients; C, A, vincristine (CAV) in 6 patients; C, A, and VP16 (CAVP16) in 5 patients. We observed 2 (7%) complete responses (CR) and 9 (33%) partial responses (PR). Duration of CRs was 8 and 14 weeks, respectively. PRs lasted a median of 22 weeks (range 16-44). Seven of 21 (33%) patients previously treated with VP16 responded to DDP plus VP16 (D-V). These results confirm D-V regimen as active in SCLC patients even when heavily pretreated. Our 33% response in patients who had VP16 in their induction treatment regimen provides further evidence of an important potentiating effect of DDP, as reported in animal system.

Antineoplastic Combined Chemotherapy Protocols↗

Phase II study of esorubicin (4'-deoxydoxorubicin) in locally advanced or metastatic head and neck carcinoma.

Sixteen patients with locally advanced or metastatic head and neck cancer were treated with esorubicin (4'-deoxydoxorubicin) at a dose of 30-35 mg/m2 i.v. every 3 weeks. One patient was lost to the follow up after one cycle, whereas in the 15 evaluable cases a total of 34 courses were administered (median per patient: 2, range: 1-6). Pretreatment for parameter lesions consisted of radiotherapy in 5, chemotherapy in 3 and both treatments in 1 patients respectively. Overall, one partial response, one stable disease and 13 progressions were documented. Severe (grade 3 and 4) leukopenia, thrombocytopenia and anemia were noted in 3, 1 and 1 patients respectively. The only patient developing leukopenia and thrombocytopenia of grade 4 subsequently died because of pneumonia. On the other hand, non-hematologic toxicity was generally mild. At this dose and schedule, esorubicin demonstrated an activity less than 20% in head and neck cancer and therefore, no further evaluation is warranted.

Aged↗

Cisplatin and 5-fluorouracil combination chemotherapy in advanced and/or metastatic colorectal carcinoma: a phase II study.

The possible synergism of cisplatin (P) and 5-fluorouracil was studied in 38 consecutive patients with advanced or metastatic colorectal carcinoma. Cisplatin 60 mg/m2 i.v.q. 4 weeks and fluorouracil 600 mg/m2 i.v. weekly were administered for at least 2 cycles, on an out-patient basis, to 24 males and 14 females with a median age of 57 years and a median PS of 80 (Karnofsky). Evaluable lesions were: primary unresectable tumor in 2 patients, local recurrence in 11, liver, lung, bone and soft tissue metastases in 21, 7, 2 and 3 patients respectively. With a median number of 3 cycles administered to 35 evaluable patients, 6 partial responses, 16 unchanged and 13 progressions were observed. Responses were observed in the liver (2 patients), lungs (1) and soft tissues (3). Median remission duration was 15 weeks, median duration of 'unchanged' was 12 weeks. The overall median survival was 24 weeks (30.5 weeks for responders and 22.5 weeks for non-responders). Six patients were pretreated with chemotherapy not containing cisplatin (mainly adjuvant 5-FU). None of them responded. Toxicity was very tolerable with moderate nausea, vomiting and alopecia in the majority of the patients; bone marrow toxicity was generally mild with no blood transfusions required, no complications of myelosuppression (sepsis or bleeding) and no chemotherapy-related deaths. In this experience the combination of low dose cisplatin with fluorouracil, does not appear to significantly enhance 5-FU toxicity and the response rate is not superior to that reported with 5-FU alone. However, better designed schedule combinations with optimal doses, sequences and exposure time of the 2-drug regimen, seem necessary to obtain the biochemical events that support the potentiation.

Adenocarcinoma↗

Non-Hodgkin's lymphomas in the elderly: prospective studies with specifically devised chemotherapy regimens in 66 patients.

The results of 2 consecutive and prospective trials with specifically devised chemotherapy regimens in elderly patients (pts) with non-Hodgkin's lymphoma (NHL) are reported. Between August 1979 and September 1984, 66 pts aged 70 or older (median 75 years) with NHL entered 2 consecutive trials, the former with single agent teniposide 100 mg/m2 i.v. weekly (41 pts), the latter with etoposide and prednimustine (E + P), 100 mg/m p.o. for 5 days every 21 days (25 pts). Forty-five pts were previously untreated, 21 previously treated. Forty-seven pts were of the intermediate and high grade groups according to the Working Formulation; 19 pts were of the low grade; 57 pts were stages III and IV, 9 pts were stages I and II. The median performance status was 70 (range 30-100). The objective response rate in the 66 evaluable pts is 53% with 38% CR; the 3-year overall, disease-free and CR survivals are 21, 12 and 40% respectively. The objective response rate in the 45 previously untreated pts is 58% with 42% CR; the 3-year overall, disease-free and CR survivals are 24, 16 and 58% respectively. The overall toxicity was mild. Severe toxicity (grade III and IV according to WHO criteria) was observed only in 16/498 courses (3.2%), with 1 toxic death (grade IV leucopenia). We experienced the usefulness of a properly orientated clinical approach to elderly pts with NHL. We suggest that a combination regimen like E + P, suitable for oral administration, may be safely employed in a large fraction of pts with NHL.

Aged↗

A phase II study of AMSA in head and neck cancer.

AMSA was given to 22 evaluable patients with advanced head and neck cancer with measurable lesions. The starting dose was 90-120 mg/m2 by i.v. infusion over 45 min every 3 weeks. The dose of AMSA was escalated by 30 mg/m2 in absence of bone marrow toxicity. At least two cycles were given prior to the evaluation of response. Only one patient with oropharyngeal cancer achieved a partial response, lasting for 20 weeks. Toxicity was mild and mainly hematological. We conclude that AMSA given at this dose and schedule has little activity in head and neck cancer.

Adult↗

Phase II study of five-day continuous infusion of vinblastine in patients with metastatic renal-cell carcinoma.

Vinblastine 5-day continuous infusion in metastatic renal-cell carcinoma was evaluated in a Phase II trial. The dosage varied from 1.4 to 1.6 mg/m2/day every 3 weeks according to previous treatment and performance status (PS). From September 1983 to January 1986, 25 consecutive patients entered the study; 21 were evaluable for response and 23 were evaluable for toxicity. The median number of cycles administered was three (range, one to six). One complete response (liver) lasting 5 months, one partial response (lung) lasting 3 months, 12 cases of stable disease, and seven progressions were noted. Toxicity (WHO criteria) was relevant and mainly hematological: one treatment-related death occurred. Vinblastine continuous infusion did not demonstrate significant antineoplastic activity against metastatic renal-cell carcinoma.

Adult↗

Lymphographic findings in prostatic carcinoma with distant metastases.

From January 1976 to December 1981, 25 patients with prostatic carcinoma and distant metastases had lymphangiography (LAG) in their initial workup either to obtain a more precise definition of tumor extension or because at the time of LAG asymptomatic metastases had not yet been detected. In 18 patients extensive bone metastases were present while in seven the only indicator of bone metastases was bone scan (limited bone disease). Positivity rate was 48% (20% in T2 cases, 53% in T3-T4; 29% in limited bone disease, 53% in extensive bone metastases). No correlation was found between LAG positivity and degree of differentiation. Patients with N0 survived longer than patients with N2-N4; however, the difference in survival is not significant and seems to be linked to the extent of bone metastases. Our data substantiate that LAG is of no value in the staging of metastatic prostatic carcinoma.

Aged↗

Randomized crossover antiemetic study in cisplatin-treated patients. Comparison between high-dose i.v. metoclopramide and high-dose i.v. dexamethasone.

This prospective, randomized, nonblind study comparing the antiemetic effectiveness of high-dose IV metoclopramide and high-dose IV dexamethasone was performed in 78 advanced cancer patients. Chemotherapeutic treatment consisted in cisplatin at a high-dose (120 mg/m2) (HD-CDDP) and at a low-dose (LD-CDDP), either alone (60 mg/m2) or in combination with other chemotherapeutic agents (50 mg/m2). The evaluation of the effectiveness of antiemetic therapy was based on three parameters: prevention of vomiting ("major protection"), number of emetic episodes, and subjective preference. Out of 78 study patients, 67 were evaluable. Overall, metoclopramide proved to be statistically superior to dexamethasone in preventing vomiting (P less than 0.005), in reducing the median/mean number of emetic episodes (P less than 0.001/0.001), and in subjective preference (P less than 0.01). The results divided between HD-CDDP and LD-CDDP groups were also in favor of metoclopramide for reduction of the median/mean number of emetic episodes (P less than 0.001/0.001 for the HD-CDDP group and P less than 0.001/0.005 for the LD-CDDP group) and in subjective preference (P less than 0.001 and P less than 0.001 for the HD- and LD-CDDP groups, respectively). No statistical differences were noted when LD-CDDP was used in monochemotherapy, whereas when LD-CDDP was used in combination chemotherapy, statistical differences in favor of metoclopramide were noted again for the median/mean number of emetic episodes (P less than 0.01/0.05) and for subjective preference (P less than 0.01), even though the effectiveness of both antiemetic agents was greatly reduced. The evaluation of previously untreated patients reflected the overall results: for the HD-CDDP group all three parameters demonstrated statistical significance in favor of metoclopramide; for the LD-CDDP group, of all three parameters, prevention of vomiting (major protection) was the only one for which there was no significant difference. Mild sedation was the only side effect of metoclopramide. No extrapyramidal reactions were noted during this trial, but concomitant orphenadrine treatment was given. Dexamethasone was always well tolerated. In conclusion, high-dose IV metoclopramide demonstrated its superiority over high-dose IV dexamethasone in all subsets of our population except the LD-CDDP monochemotherapy group, in which the two antiemetics were found to be equivalent in effect.

Adult↗

Teniposide is not effective in chronic lymphocytic leukemia.

Teniposide has been evaluated in a phase II clinical trial in chronic lymphocytic leukemia (CLL). Among 16 consecutive patients with CLL entered in the study and treated with Teniposide, 100 mg/m2 weekly, no objective response was observed. Toxicity was generally mild and mainly hematologic. Teniposide at this dosage and schedule is an inactive drug in CLL.

Adult↗

Combination chemotherapy with fluorouracil, adriamycin, cis-platinum and VM-26 in advanced transitional cell carcinoma of the urinary tract.

From October 1981 to October 1984, 42 consecutive patients with locally advanced unresectable or metastatic transitional cell carcinoma of the urinary tract were treated with cis-Platinum 50 mg/m2 i.v. and Adriamycin 50 mg/m2 i.v. day 1, and Fluorouracil 500 mg/m2 i.v. and VM26 100 mg/m2 days 1 and 8, every 3 weeks. In the 36 evaluable patients, 4 complete remissions and 15 partial remissions were noted (52.7% response rate). Of the 12 patients with previously untreated, locally advanced bladder carcinoma, 8 responded, with 3 pathologically confirmed complete remissions. Toxicity was moderate. Median survival was 44 weeks. This 4-drug combination had significant palliative activity in our patient population. Its role in the preoperative setting deserves further evaluation.

Adult↗

Phase II trial of oral VP 16-213 (etoposide) in patients with advanced head and neck cancer.

We tested VP 16-213 in 16 patients with advanced head and neck cancer after conventional treatments. VP 16-213 was administered orally at the dosage of 100 mg/mq for 5 consecutive days every 3 weeks. No patient achieved an objective response. Toxicity was mild. VP 16-213 given at this dose and schedule revealed no activity in pretreated patients with head and neck cancer.

Aged↗

Phase II study of teniposide (VM-26) in multiple myeloma.

From September 1979 to December 1983, a phase II trial with teniposide (VM-26) in multiple myeloma (MM) was conducted at our institution. Of the 30 patients entered, 25 were evaluable for response, 12 previously treated with M-2 protocol and 13 previously untreated elderly (greater than or equal to 70 years) patients. A median of nine cycles (range 1-21) of VM-26 was administered. Seven responses (28%) according to Myeloma Task Force criteria were observed with a median duration of 4 months (range 2-12+). Four responses (33%) were observed in the 12 previously treated patients. Overall toxicity was mild. VM-26 seems an active drug in MM, without significant toxicity even in elderly patients.

Adult↗

High-dose versus low-dose cisplatin in advanced head and neck squamous carcinoma: a randomized study.

From November 1981 to February 1983, 64 patients with advanced head and neck squamous carcinoma were randomly treated with either high-dose (120 mg/m2) or low-dose (60 mg/m2) cisplatin. Of the 62 eligible patients, 59 were evaluable: the response rate observed in patients receiving high-dose and low-dose cisplatin was 16.1% and 17.8%, respectively. Survival was superimposable in the two treatment arms. No evidence of dose dependency of cisplatin activity in advanced head and neck squamous carcinoma was noted in this randomized trial.

Carcinoma, Squamous Cell↗