Search PubMed⌕ Search

Biomedical subjects

G Cocconi

Publications and source records attributed to G Cocconi.

At least 19 recordsLinked to original sources
PubMed2000

Vinorelbine combined with paclitaxel infused over 96 hours (VI-TA-96) for patients with metastatic breast carcinoma.

BACKGROUND: Vinorelbine (VI) and paclitaxel (TA) are among the most active single agents in the treatment of patients with breast carcinoma, and both have microtubules as their cytotoxic target. This Phase I-II study combined these 2 agents and used a 96-hour intravenous (i.v.) infusion of paclitaxel to maximize their cytotoxic activities. METHODS: Patients with metastatic breast carcinoma who were previously treated with chemotherapy were administered increasing doses of a 96-hour paclitaxel i.v. infusion from Days 1 to 5, with a first fixed dose of vinorelbine (12.5 mg/m(2) on Days 1 and 5) every 3 weeks. The dose of paclitaxel was then decreased starting from the previously established tolerated dose, and a second fixed dose of vinorelbine (15 mg/m(2) on Days 1 and 5) was given. This identified 2 acceptable doses of paclitaxel (110 mg/m(2) with VI 12.5 mg/m(2) and 90 mg/m(2) with VI 15 mg/m(2)). The latter was used in the subsequent Phase II study. RESULTS: For the 50 patients treated with any dose, the complete response (CR) and the CR plus partial response (PR) rates were, respectively, 14% and 48% (95% confidence interval [CI], 34-67%). When only the 27 patients treated with the Phase II dose were considered, the figures were, respectively, 11% and 52% (95% CI, 42-62%). The median time to progression was 26 weeks, and the median survival 51 weeks. The dose-limiting toxicity was febrile neutropenia. CONCLUSIONS: At the dose schedule identified for the Phase II study, the VI-TA-96 combination has considerable antitumor activity; pharmacoeconomic interest (it requires about half the doses of the agents administered singly); no major toxicity, except G4 neutropenia; and no need for premedication. This combination may be recommended as one of the most effective therapeutic options for patients with metastatic breast carcinoma who were pretreated mainly with anthracycline-containing chemotherapy.

Adult↗
PubMed2000

Comparison of the results of immunocytochemical assays for biologic variables on preoperative fine-needle aspirates and on surgical specimens of primary breast carcinomas.

BACKGROUND: Fine-needle aspiration biopsy (FNAB) is a well-documented procedure for the diagnosis and biologic characterization of breast carcinoma. In order to compare the immunocytochemical expression of biologic parameters on cytology and on histology, estrogen receptor (ER) and progesterone receptor (PgR) status, p53 protein expression, and Ki67 growth fraction were evaluated on presurgical fine-needle aspirates (FNAs) from breast carcinoma patients and on the corresponding surgical samples prior to any systemic therapy. METHODS: FNAs were performed on 104 patients with primary breast carcinoma at the time of diagnosis and subjected to immunocytochemical evaluation of ER, PgR, p53, and Ki67. The same parameters were immunohistochemically evaluated on the corresponding paraffin embedded sections. RESULTS: ER, PgR, p53, and Ki67 were evaluable on FNAs and on paired tissue sections in 100, 97, 68, and 84 cases, respectively. Concordance between cytology and histology was 89% for ER, 78% for PgR, 79% for p53, and 70% for Ki67. CONCLUSIONS: The concordance between the results of immunocytochemical evaluation of ER, PgR, p53, and Ki67, on both cytology and histology, underscores the reliability of the biologic characterization of breast carcinoma by FNAB. This approach could be particularly useful in predicting prognosis and response to treatment in patients who are candidates for neoadjuvant chemotherapy and/or endocrine therapy.

Biomarkers↗
PubMed2000

Biological variables in non-small cell lung cancer: comparison between immunocytochemical determination on fine needle aspirates from surgical specimens and immunohistochemical determination on tissue sections.

A number of biological and predictive markers of non-small cell lung cancer (NSCLC) have been sought, but these have so far been mainly evaluated on surgically resected specimens. Given that fine needle aspiration biopsy (FNAB) is being increasingly used in the diagnosis of NSCLC, its application could be extended to the immunocytochemical detection of biological parameters at the time of diagnosis before surgery. In order to assess the reliability of estimating biological markers on fine needle aspirates (FNAs) from NSCLC, the aim of this study was to compare Ki67 growth fraction, p53 and bcl-2 protein expression as revealed by the immuncytochemical assessment of FNAs obtained from surgical samples with the immunohistochemical results obtained from the corresponding histological sections. FNAs were performed on surgical specimens obtained from 29 NSCLC patients. Ki67, p53 and bcl-2 were cytologically and histologically evaluable in respectively 25, 27 and 19 cases. Concordance between FNAs and corresponding paraffin sections was 84% for Ki67, 93% for p53 and 95% for bcl-2. All of the specimens whose biological parameters were studied by immunocytohistochemistry also underwent flow cytometric DNA analysis of FNAs taken from fresh surgical specimens. Of the 29 cases, 22 were aneuploid and seven diploid. The S-phase fraction (SPF) was evaluable in 62% of cases. Comparison of SPF results on FNAs with Ki67 values evaluated on the corresponding histologic and cytologic specimens, revealed a significant correlation only with histology. Good reproducibility was also found in relation to the immunocytochemical results obtained on FNAs from different areas of the same tumour, showing that tumour heterogeneity does not affect the method. The concordance between the immunocytochemical and immunohistochemical results suggests that FNAB may be a reliable procedure for the biological characterization of NSCLC. Given its limited invasiveness, FNAB could be used in vivo for the preoperative assessment of biological parameters in patients with operable or metastatic NSCLC.

Biomarkers, Tumor↗
PubMed1999

Author reply

Explore the source record for details and available documents.

Journal Article↗
PubMed1999

Bcl-2 expression on fine-needle aspirates from primary breast carcinoma: correlation with other biologic factors.

BACKGROUND: The bcl-2 gene encodes for a protein that is involved in cell death regulation. It frequently is expressed in breast tumors, in which it is associated with favorable prognostic factors. It has been suggested that bcl-2 also may act as a modulator of response to chemotherapy and/or endocrine therapy. Because fine-needle aspiration (FNA) biopsy has been established as a reliable method for the diagnosis and biologic characterization of breast carcinoma, we assessed Bcl-2 expression on FNAs from primary breast carcinoma and evaluated its correlations with other prognostic variables. METHODS: Bcl-2, estrogen receptor (ER), progesterone receptor (PgR), p53 protein expression, and Ki-67 growth fraction were evaluated by immunocytochemistry on FNAs from 130 patients with primary breast carcinoma. Nuclear cytologic grade was assessed on FNA smears. RESULTS: Bcl-2 was expressed in 99 of 130 FNAs (76%). Bcl-2 expression was correlated with positive ER (P < 0.001) and PgR (P < 0.001) status and inversely correlated with p53 (P = 0.0036), Ki-67 (P = 0.0073), and nuclear cytologic grade (P < 0.001). CONCLUSIONS: Bcl-2 expression, evaluated by immunocytochemistry on FNAs from primary breast carcinoma, correlates with favorable prognostic features such as ER and PgR expression, p53 negativity, a low Ki-67 index, and high tumor differentiation. These results are in agreement with those found on histologic samples. As FNA biopsy is used increasingly as a primary tool in the diagnosis of breast carcinoma, Bcl-2 evaluation by immunocytochemistry on FNA may provide, in addition to other biologic variables, useful information for prognostic and predictive purposes, particularly in patients considered to be candidates for neoadjuvant treatments. Cancer (Cancer Cytopathol)

Biomarkers, Tumor↗
PubMed1999

Patients' opinions, feelings, and attitudes after a campaign to promote the Di Bella therapy.

BACKGROUND: An emotional campaign promoting the Di Bella cancer therapy was launched by the Italian media in 1997. Its effects on patients' hopes, feelings, and decision-making processes were largely unknown. We undertook an investigation of this issue. METHODS: Between Feb 25 and March 31, 1998, a ten-item questionnaire was distributed to 1300 unselected adult patients attending 13 cancer centres throughout Italy. Four expert psycho-oncologists reviewed the design and validity of the contents of the questionnaire. Sociodemographic information was also collected. FINDINGS: 1120 (86%) questionnaires were returned and analysed. The main sources of information were television/radio (62%) and newspapers (26%); only 5% cited doctors. The campaign induced optimism in the patients about the efficacy of the method (ineffective 1%, effective 42%, uncertain 57%), and 53% said their hope of cure was increased. However, 48% felt more confused. 24% do not discuss new treatments with their oncologists, and 20% would like to but cannot. When choosing a treatment, the advice of a trusted doctor was judged more important than scientific progress (53% vs 32%) and 63% would try even unproven treatments in the hope of a cure. Replies to many of the questions were influenced by patients' educational attainment and by the degree of communication with their oncologists. INTERPRETATION: Science cannot prevent the harm caused by such campaigns and their psychological consequences, particularly for less educated patients. When making decisions, patients are looking for hope from the treatment and trust in their doctor, both of which depend on effective doctor-patient communications that therefore need to be improved.

Clinical Trials, Phase II as Topic↗
PubMed1999

Front-line chemotherapy with cisplatin and etoposide for patients with brain metastases from breast carcinoma, nonsmall cell lung carcinoma, or malignant melanoma: a prospective study.

BACKGROUND: The conventional treatment of brain metastases not amenable to surgery is most often radiotherapy. Until now, pharmacologic issues related to the blood brain barrier (BBB) prevented a wide evaluation of chemotherapy. The authors previously reported that the combination of cisplatin (P) and etoposide (E) had strikingly high activity in patients with brain metastases from breast carcinoma. The purpose of this study was to assess, in a larger prospective study, the front-line activity of that combination against brain metastases from breast carcinoma (BC), nonsmall cell lung carcinoma (NSCLC), and malignant melanoma (MM) in patients previously untreated with radiotherapy. METHODS: From December 1986 to July 1993, 116 patients received P 100 mg/m2 on Day 1 and E 100 mg/m2 on Days 1, 3, and 5 or on Days 4, 6, and 8 every 3 weeks. An insignificant change in the E schedule using the same dose on a random basis assured the prospective enrollment and the registration of all cases. Six patients were not eligible and three patients were excluded from the analysis because they were lost to follow-up shortly after the date of registration. One-hundred seven patients were considered for analysis. The distribution according to the primary tumor site was BC in 56 patients (52%), NSCLC in 43 (40%), and MM in 8 (8%). The first evaluation of response was performed after two cycles. In cases of no disease progression, chemotherapy was continued to a maximum of six cycles. RESULTS: Among the 56 patients with BC, 7 achieved complete response (CR) (13%), 14 achieved partial response (PR), 12 had no change (NC), 15 had progressive disease (PD), and 8 had insufficient treatment or response was not assessed. The CR plus rate was 38%. Among the 43 patients with NSCLC, 3 achieved CR (7%), 10 achieved PR, 15 had SD, 7 had PD, and 8 had insufficient treatment or response was not assessed. The CR plus PR rate was 30%. None of the eight patients with MM achieved an objective response. The median survival was 31 weeks for patients with BC (range, 0-287), 32 for patients with NSCLC (0-392+), and 17 for patients with MM (2-48). CONCLUSIONS: The combination of P and E is effective for patients with brain metastases from BC and NSCLC. In this study, the response rate was of the same order as that reported for disseminated disease without central nervous system involvement. The survival figures compare favorably with some others reported in the literature for patients given radiotherapy. A randomized study is warranted to compare this chemotherapy followed by radiotherapy with radiotherapy alone for patients with brain metastases from BC or NSCLC not amenable to surgery or radiosurgery.

Adult↗
PubMed1999

Three new active cisplatin-containing combinations in the neoadjuvant treatment of locally advanced and locally recurrent breast carcinoma: a randomized phase II trial.

We designed three new four-drug cisplatin-containing combinations and evaluated their activity in a randomized phase II study including patients with locally advanced (stage III) and locally recurrent breast carcinoma. All combinations included methotrexate (M) on day 1 and cisplatin (P) on day 2 (MVAC-like combinations) and differed from one another by the addition of Epirubicin (Epi), Vincristine (V), Etoposide (E), Mitomycin (Mi). Based on the administered agents, they were named MPEMi, MPEpiE, MPEpiV. The combinations were randomly assigned to 101 patients, 57 with locally advanced and 44 with locally recurrent breast carcinoma. Response was evaluated after 4 cycles. The complete response (CR) rates were 7% and 43% and the CR plus partial response (PR) rates were 84% and 89% in locally advanced and in locally recurrent disease, respectively. In locally advanced disease, a pathologic CR (pCR) was assessed in seven of 57 patients (12%). There were no significant differences among the three combinations. The toxicities were at times severe, but generally tolerable, as demonstrated by the high cumulative doses of the drugs received by the patients. In conclusion, these three innovative chemotherapy regimens induced high CR plus PR rates in the neoadjuvant treatment of stage III and of locally recurrent breast carcinoma, and a high rate of pCR in stage III disease. These regimens warrant testing in phase III trials.

Adult↗
PubMed1999

Mature results of a prospective randomized trial comparing a three-weekly with an accelerated weekly schedule of cisplatin in advanced ovarian carcinoma.

In a retrospective analysis of a series of clinical trials by Levin and Hryniuk in 1987, the average relative dose intensity of first-line chemotherapy for advanced ovarian cancer correlated significantly with clinical response and survival, and cisplatin was the only drug for which the outcome correlated with the individual drug relative dose intensity. There was a need to test whether and to what extent this evidence would be confirmed in a prospective evaluation. In this study 101 patients with advanced ovarian carcinoma were randomized to receive the same total dose of cisplatin but at the conventional 3-weekly schedule (CTWS) (100 mg/m2 every 3 weeks for six cycles) (51 patients) or at an experimental accelerated weekly schedule (AWS) (100 mg/m2 every week for two triplets of three cycles separated by a 5-week interval) (50 patients). To benefit from a multidrug regimen at the same extent, patients in both arms sequentially received four cycles of doxorubicin and cyclophosphamide. The median follow-up period of this study is 9.7 years. In 42 and 40 patients of the two arms having evaluable response, the clinical complete response rates to cisplatin were 14% and 22% and the complete plus partial response rates were 48% and 55% in the CTWS and in the AWS arm, respectively. These differences were not statistically significant. However, the survival curves were similar during the first 2 years but clearly diverged thereafter in favor of the AWS arm (p = 0.07). At 5 years, 12% and 30% of the patients were still alive in the CTWS and in the AWS arm, respectively. Hematologic toxicity was not relevant in either arm of the study. Nonhematologic toxicity, especially ototoxicity, was substantial and significantly higher in the AWS arm. Although statistically nonsignificant, this AWS regimen of cisplatin is associated with long-term better survival compared to the CTWS regimen in advanced ovarian carcinoma. This accelerated approach administering cisplatin should be further investigated, especially in patients with low residual disease after primary surgery.

Adult↗
PubMed1999

Comparison of CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) with a rotational crossing and a sequential intensification regimen in advanced breast cancer: a prospective randomized study.

The Italian Oncology Group for Clinical Research tested two experimental chemotherapy strategies in an attempt to improve the results achievable with conventional chemotherapy in metastatic breast cancer. One hundred sixty-two patients were randomly allocated as follows: (a) to the conventional cyclophosphamide, methotrexate, 5-fluorouracil chemotherapy regimen (CMF); (b) to a rotational crossing program (ROT-CROSS); or (c) to a sequential intensification program (SEQ-INT). The same single agents (C, M, F, cisplatin, etoposide, and doxorubicin) were administered in both experimental arms, but following a different policy. The SEQ-INT program induced a significantly higher complete response (32% vs. 6%, p = 0.0006) and objective response rate (72% vs. 42%, p = 0.0047) than CMF did. There were no differences in survival between CMF and either experimental arm. A number of side effects were significantly more with both experimental chemotherapies than with CMF, but the treatments were generally tolerable. Although some caution is required when interpreting a significant advantage found between an entire chemotherapeutic strategy and a single conventional combination, this study documents the potential therapeutic advantage of administering different sequential chemotherapies, and changing each at the time of maximum result without waiting for a progression. The impressive cytoreductive effects achievable with this policy (SEQ-INT) in metastatic disease merit further investigation in the adjuvant setting.

Adenocarcinoma↗
PubMed1998

Doxorubicin vs epirubicin, report of a second-line randomized phase II/III study in advanced breast cancer. EORTC Breast Cancer Cooperative Group.

The EORTC Breast Cancer Cooperative Group carried out a randomized trial to compare doxorubicin with epirubicin as second-line chemotherapy in patients with metastatic breast cancer. Two hundred and fifty-nine patients with at least one site of metastatic disease entered this trial, of whom 232 patients were eligible. Treatment consisted of doxorubicin 75 mg m(-2) or epirubicin 90 mg m(-2) i.v. every 3 weeks. The overall response rates for doxorubicin and epirubicin were 36% and 28% respectively (P = 0.173). The median time to progression was 23 weeks for doxorubicin and 19 weeks for epirubicin (P = 0.063) and the median duration of response was 40 weeks for doxorubicin and 32 weeks for epirubicin (P = 0.059). The median survival was 47 weeks for doxorubicin and 44 weeks for epirubicin (P = 0.196). Leucocyte count on retreatment day (P = 0.011) and platelet nadir (P = 0.031) were significantly lower in the doxorubicin-treated group. Also mucositis (P < 0.001), diarrhoea (P = 0.005) and haemorrhage (P = 0.048) were significantly worse in the doxorubicin arm. Nine patients on doxorubicin and two patients on epirubicin experienced congestive heart failure (CHF). At the dose levels used in this study, no statistical differences in response rate and survival were found between the two treatment arms. Treatment with doxorubicin tended to result in a slightly longer duration of response and time to progression but doxorubicin was more toxic than epirubicin.

Adult↗
PubMed1998

Open, randomized, multicenter trial of raltitrexed versus fluorouracil plus high-dose leucovorin in patients with advanced colorectal cancer. Tomudex Colorectal Cancer Study Group.

PURPOSE: To compare raltitrexed (Tomudex; Zeneca Pharmaceuticals Ltd, Macclesfield, United Kingdom) a direct, specific thymidylate synthase (TS) inhibitor with fluorouracil (5-FU) plus high-dose leucovorin (LV) as first-line treatment for advanced colorectal cancer (ACC). PATIENTS AND METHODS: A total of 495 patients were randomized to raltitrexed (3 mg/m2) once every 3 weeks or 5-FU (400 mg/m2) plus LV (200 mg/m2) daily for 5 days every 4 weeks. RESULTS: The randomized groups were well balanced demographically. With a minimum 17-month follow-up, median survival was comparable between groups (10.9 months raltitrexed v 12.3 months 5-FU/LV; hazards ratio, 1.15; 95% confidence interval [CI], 0.93 to 1.42; P=.197), although time to progression was statistically significantly shorter in the raltitrexed group. Overall objective responses were comparable (19% raltitrexed v 18% 5-FU/LV), with more than 50% of patients in each group having stable disease. Significantly less World Health Organization (WHO) grade 3 and 4 stomatitis (2% v 16%, P < .001) and a reduced incidence of leukopenia (6% v 13%) and diarrhea (10% v 19%) occurred in the raltitrexed group (particularly at cycle 1 ). This resulted in fewer dose reductions at cycle 2 (4% raltitrexed v 28% 5-FU/LV) and early quality-of-life (QoL) benefits for raltitrexed patients. Reversible, clinically insignificant increases in transaminases were reported in 13% of raltitrexed patients. Palliative benefits of weight gain, improved performance status, and reduced disease-related symptoms were evident in both groups. CONCLUSION: Raltitrexed is confirmed as an effective option in the first-line palliative management of ACC, with comparable efficacy to and tolerability advantages (in terms of reduced incidence of stomatitis, diarrhea, and leukopenia) over 5-FU/LV. Raltitrexed has the added convenience of an every 3 weeks dosing schedule.

Adenocarcinoma↗
PubMed1997

Comparison between Ki-67 index and S-phase fraction on fine-needle aspiration samples from breast carcinoma.

BACKGROUND: Fine-needle aspiration (FNA) biopsy has been used increasingly in the diagnosis and biologic characterization of breast carcinomas in patients who receive preoperative chemotherapy. Because proliferative activity of breast carcinoma has been shown to be of prognostic significance, the authors compared immunocytochemical Ki-67 growth fraction and flow cytometric S-phase fraction (SPF), both evaluated on FNA samples. METHODS: The proliferative activity of 134 FNA samples from primary breast carcinoma patients was studied using both immunocytochemistry with the monoclonal antibody Ki-67 and SPF determined by DNA flow cytometry. RESULTS: Ki-67 and SPF were evaluable in 114 and 107 cases, respectively, and both were evaluable in 95 cases. Of the 134 FNA samples studied, 37% were diploid and 63% were aneuploid. The distribution of both Ki-67 and SPF was different in diploid and aneuploid tumors. The median Ki-67 value as well as the median SPF were significantly higher in aneuploid versus diploid tumors (P < 0.001). Median Ki-67 and SPF values were used to discriminate between low versus high proliferating tumors. The overall concordance between Ki-67 and SPF was 75% (P < 0.001). A good correlation was found between Ki-67 and SPF (correlation coefficient = 0.72; P < 0.001). CONCLUSIONS: The results of the current study suggest that Ki-67 growth fraction and SPF determined by FNA may be used as measurements of the proliferative activity of breast carcinoma. The authors recommend these determinations be used as preoperative procedures in patients with a cytologic diagnosis of breast carcinoma who are candidates for neoadjuvant chemotherapy and/or endocrine therapy.

Antibodies, Monoclonal↗
PubMed1997

Double-blind, multicenter, randomized trial to compare the effect of two doses of adrenocorticotropic hormone versus placebo in controlling delayed emesis after high-dose cisplatin in adult patients with cancer.

PURPOSE: To compare, in a double-blind, placebo-controlled, randomized trial, the efficacy of two different doses of the depot formulation of adrenocorticotropic hormone (ACTH) in controlling delayed emesis after cisplatin. PATIENTS AND METHODS: One hundred fifty-two patients were enrolled onto the study. On day 1, all patients received cisplatin (60 to 120 mg/m2) and a combination of dexamethasone 20 mg plus ondansetron or metoclopramide to prevent acute emesis. On day 2 (24 hours after cisplatin administration), patients were randomized to receive placebo, or ACTH 1 mg intramuscularly (I.M.), or ACTH 2 mg I.M. plus one additional dose of 1 mg on day 4. Details of vomiting, nausea, and adverse effects were recorded daily for every 24-hour period from day 2 to day 6. In a subset of patients, serum cortisol levels were measured between 20 and 72 hours after cisplatin administration. RESULTS: One hundred fifty patients were assessable. Over the 5 days of the study, delayed vomiting occurred less frequently in the patients treated with ACTH 2 mg plus 1 mg than in those treated with ACTH 1 mg or placebo (28%, 38%, and 65%, respectively; P = .001). The greatest observed differences were seen on days 2 (24 to 48 hours; P = .01) and 3 (48 to 72 hours; P = .01). On days 4, 5, and 6 (96 to 144 hours), no significant differences were observed among the three arms. The severity of delayed emesis expressed as the mean number of emetic episodes per day was 0.48, 0.70, and 0.80, respectively (P = .002). Patients treated with the higher dose of ACTH had the least nausea on day 3 (P = .02) and day 4 (P = .03). Adrenal cortisol secretion rapidly increased after ACTH injection, but was suppressed for approximately 44 hours in the placebo group. Toxicity was mild and transient in all groups. CONCLUSION: ACTH reduces the incidence and severity of delayed vomiting and nausea after cisplatin. A dose of 2 mg 24 hours after cisplatin is better than one of 1 mg. Whether the activity of ACTH is mediated only by adrenal corticosteroids needs to be verified.

Adrenocorticotropic Hormone↗
PubMed1996

The combination of cisplatin, doxorubicin, and mitomycin (PAM) compared with the FAM regimen in treating advanced gastric carcinoma. A phase II randomized trial of the Italian Oncology Group for Clinical Research.

BACKGROUND: In a randomized Phase II study, the authors evaluated the activity and toxicity of the new cisplatin, doxorubicin, and mitomycin C (PAM) combination, that includes cisplatin (P) instead of 5-fluorouracil as in the 5-fluorouracil, doxorubicin, and mitomycin C (FAM) combination, in patients with advanced gastric carcinoma. FAM was utilized as a control treatment arm. METHODS: Fifty eligible patients were assigned to the FAM (5-fluorouracil 600 mg/m2 intravenous (i.v.) on Days 1, 8, 29, 36; doxorubicin 30 mg/m2 i.v. on Days 1 and 29; mitomycin C 10 mg/m2 i.v. on Day 1; every 8 weeks) and 52 to the PAM combination (cisplatin 60 mg/m2 i.v. on Days 1 and 29; doxorubicin 30 mg/m2 i.v. on Days 1 and 29; mitomycin C 10 mg/m2 i.v. on Day 1; every 8 weeks). All eligible patients were included in the evaluation of response, toxicity and survival. RESULTS: The PAM combination complete response (CR) rate was 8%, and the CR plus partial response (PR) rate was 21% (95% confidence interval [CI] from 10% to 32%). The median time to progression, duration of response, and duration of survival were 15, 26, and 29 weeks, respectively. The FAM combination CR rate was 2% and the CR plus PR rate was 26% (95% CI from 14% to 38%). The median time to progression, duration of response, and duration of survival were 17, 27, and 23 weeks, respectively. Hematologic and nonhematologic toxicity were mild with both regimens. CONCLUSIONS: This study shows that this new combination, that does not include 5-fluorouracil, is active in patients with advanced gastric carcinoma. Since treatment with 5-fluorouracil alone is still considered the standard according to some authors, the PAM combination may be included among the sequential clinical options before or after treatment with 5-fluorouracil alone.

Adult↗
PubMed1996

Nuclear grading and flow cytometric DNA pattern in fine-needle aspirates of primary breast cancer.

Fine-needle aspiration (FNA) biopsy is increasingly used in the diagnosis and biological characterization of breast carcinomas in patients who receive preoperative chemotherapy. In this context, nuclear cytologic grade supplemented by DNA content could play an important role in the morphologic assessment of breast cancer. In this study, DNA ploidy pattern, analyzed by flow cytometry on FNAs from 92 primary breast carcinomas, was related to cytologic nuclear grade. Twenty-seven samples were cytologic grade 1, 33 were grade 2, and 32 were grade 3. Ploidy correlated with cytologic nuclear grade (P = 0.0001). Thirty percent of grade 1, 55% of grade 2, and 84% of grade 3 tumors were DNA aneuploid. For 30 of the 92 FNAs, it was possible to compare nuclear cytologic grade with the corresponding histologic grade using the Scarff, Bloom, and Richardson system. A high concordance (80%) between nuclear grade on FNAs and histologic grade was found. DNA flow cytometry in combination with nuclear cytologic grade might represent additional information for the characterization of breast cancer diagnosed by FNA.

Biopsy, Needle↗
PubMed1996

Letrozole, a new oral non-steroidal aromastase inhibitor in treating postmenopausal patients with advanced breast cancer. A pilot study.

PURPOSE: To evaluate the endocrine effects as well as the pharmacokinetic parameters, efficacy and safety of letrozole, a new fourth-generation non-steroidal aromatase inhibitor. PATIENTS AND METHODS: Fourteen postmenopausal women with progressive metastatic breast cancer, previously treated with endocrine therapy and/or chemotherapy for advanced disease, were treated with 0.5 mg daily doses of letrozole, orally. Endocrine and pharmacokinetic measurements were made before treatment and on days 14, 28, 56, and 84 of therapy. RESULTS: Letrozole induced a >86% decrease in plasma estrone and a approximately 67% reduction in circulating estradiol from day 14 on. There was a statistically significant decrease in plasma cortisol, which appeared clinically irrelevant since all values remained within the normal range. No significant changes in aldosterone concentration were noted. One patient achieved a complete response (CR) and 4 patients a partial response (PR), with an objective response rate of 36% (95% CI 13% to 65%). Median duration of response was 24 months, ranging from 4 to 44 months. No toxic effects attributable to letrozole were noted in any patient. CONCLUSION: Letrozole appears to be a very promising new antiaromatase drug. The characteristics of the patients more likely to respond, taking into account prior systemic treatment, should be defined by future studies. Further phase II and phase III studies comparing letrozole to other available second or even first-line endocrine-therapy agents, are warranted.

Adult↗