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M Merlano

Publications and source records attributed to M Merlano.

At least 19 recordsLinked to original sources
PubMed2004

Phase II study of cisplatin, gemcitabine and 5-fluorouracil in advanced pancreatic cancer.

BACKGROUND: The aim of this study was to determine the activity of the combination of cisplatin, gemcitabine and 5-fluorouracil (5-FU) as therapy for metastatic or locally advanced inoperable pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients with histologically proven advanced or metastatic pancreatic adenocarcinoma received first-line chemotherapy comprising cisplatin (20 mg/m2 on days 1, 8, 15, 22, 29 and 36), gemcitabine (1000 mg/m2 on days 1, 8, 29 and 36) and 5-FU (200 mg/m2 as continuous infusion on days 1-42) every 56 days. RESULTS: A total of 34 patients were studied. Eighty courses were administered (median two courses per patient). Among 32 patients evaluable for response, two patients had a complete response and four a partial response for an overall response rate of 19% (95% confidence interval 7% to 36%). Thirteen patients had stable disease (40%) and 13 progressed. Median progression-free survival was 4.7 months, median survival 9.0 months and 26% of patients achieved 1-year survival. Ten of 25 patients (40%) with pain at presentation had a sustained reduction of analgesic consumption. The principal grade 3/4 toxicities were neutropenia, thrombocytopenia, anaemia and mucositis, occurring in 24%, 21%, 9% and 3% of patients. CONCLUSION: This schedule seems well tolerated and active in pancreatic cancer and worthwhile of further evaluation.

Adult↗
PubMed2002

Phase I, dose-finding study of capecitabine in combination with docetaxel and epirubicin as first-line chemotherapy for advanced breast cancer.

PURPOSE: Capecitabine is an oral fluoropyrimidine with considerable activity and minimal myelosuppression and alopecia. This phase I study evaluated the addition of capecitabine to epirubicin/docetaxel combination therapy as first-line treatment for advanced breast cancer. PATIENTS AND METHODS: Twenty-three female patients with advanced breast cancer received capecitabine (765-1060 mg/m2 twice daily on days 1-14 of a 3-week treatment cycle) in combination with epirubicin and docetaxel (75 mg/m2 i.v. on day 1). RESULTS: The maximum tolerated dose of capecitabine was 985 mg/m2 and the principal dose-limiting toxicity was febrile neutropenia. No grade 3/4 anemia or thrombocytopenia occurred. There were no grade 4 non-hematological events and grade 3 events other than alopecia were rare. Alopecia occurred in all patients and treatment cycles, and asthenia occurred in all patients and in 84% of treatment cycles. Other frequent adverse events included nausea, vomiting, fever, paresthesia and elevated transaminase levels. An objective response to treatment was observed in 91% (95% confidence interval 72% to 99%) of patients. CONCLUSIONS: The addition of capecitabine to docetaxel/epirubicin combination therapy provides a well-tolerated and active first-line chemotherapy regimen in patients with advanced breast cancer, and merits phase II/III evaluation.

Adult↗
PubMed2001

Alternating chemoradiotherapy versus partly accelerated radiotherapy in locally advanced squamous cell carcinoma of the head and neck: results from a phase III randomized trial.

BACKGROUND: The authors previously have found that in patients with locally advanced squamous cell carcinoma of the head and neck (SCC-HN), alternating chemoradiotherapy (ALT) was superior to low-total-dose conventional radiotherapy alone. The purpose of this randomized trial was to compare the same chemoradiotherapy approach with high-total-dose partly accelerated radiotherapy. METHODS: During 6 years, 136 consecutive patients with previously untreated unfavorable Stage II or Stage III-IV (International Union Against Cancer) SCC of the oral cavity, pharynx, and larynx were enrolled. They were randomly assigned to chemotherapy consisting of 4 cycles of intravenous cisplatin (20 mg/m(2) of body surface area per day for 5 consecutive days) and 5-fluorouracil (200 mg/m(2) per day for 5 consecutive days; weeks 1, 4, 7, and 10) alternated with three 2-week courses of radiotherapy (20 grays [Gy] per course, 2 Gy per day, 5 days per week; ALT, 70 patients) or to partly accelerated radiotherapy with final concomitant boost technique (75 Gy/40 fractions in 6 weeks; partly accelerated radiotherapy [PA-RT], 66 patients). RESULTS: At the median follow-up of 60 months (range, 30-102 months), no statistical differences were observed in overall survival, progression free survival, or locoregional control between the 2 treatments. Actuarial 3-year overall survival and progression free survival were 37% and 35%, respectively, in the ALT group and 29% and 27%, respectively, in PA-RT group. The median overall survival and progression free survival were 24 and 15 months, respectively, in the ALT arm and 18 and 11 months, respectively, in PA-RT arm. Actuarial 3-year locoregional control rates were 32% in the ALT group and 27% in the PA-RT group. At multivariate analysis, tumor classification was the only factor that emerged as a significant independent variable affecting overall survival. Patients treated in the PA-RT arm experienced higher Grade 3+ (World Health Organization) acute skin and mucosal reactions than patients in the ALT arm. Moreover, local late mucosal and skin toxicities occurred more often in patients treated with PA-RT. CONCLUSIONS: This trial failed to disclose statistically significant differences in the outcome of patients treated with either ALT or PA-RT. Therefore, definitive conclusions could not be made. However, acute skin effects and late mucosal and skin toxicities above the clavicles appeared to be significantly lower with chemoradiotherapy.

Aged↗
PubMed2001

Best supportive care in non-small cell lung cancer: is there a role for radiotherapy and chemotherapy?

Best Supportive Care (BSC) is the treatment of choice when cure is not achievable with anticancer treatments and involves management of disease-related symptoms. In the palliative treatment of non-small cell lung cancer (NSCLC) radiation therapy has for a long time been the cornerstone of symptom management, although the best schedule is still to be defined. Chemotherapy, on the other hand, has been excluded from classical definitions of BSC and has been reserved only for selected patient populations in which a survival benefit was demonstrated using cisplatin-based regimens. We reviewed randomized trials on both palliative radiotherapy and chemotherapy in order to assess the impact of anticancer treatments on quality of life in advanced NSCLC patients. While no randomized trials compared radiation therapy with a control arm not including it, several randomized trials assessed the use of different schedules. Hypofractionated schedules seem to have comparable palliative activity when compared with the standard fractionated regimens, at least in metastatic, poor-prognosis patients. In locally advanced, inoperable NSCLC higher radiation doses administered with conventional fractionation achieve better results in terms of local control and survival. The rate of palliation of local symptoms is high, being 60-80% for chest pain and hemoptysis, while breathlessness and cough are controlled at a somewhat lower rate (50-70%). General symptoms (fatigue, anorexia, and depression) are affected in a minority of patients. Chemotherapy was compared with BSC in several randomized trials, in some of which an analysis of the quality of life was included. Results are consistent in favor of its palliative role and, when local symptom control is assessed, rates of palliation seem similar to those achieved by radiation. Benefits apply to metastatic NSCLC patients with good performance status, low body weight loss, age below 70-75. However, some studies support the use of chemotherapy also in patients with poor prognostic features. A comparison in terms of quality of life and symptom palliation between different chemotherapy regimens is the object of few trials. Both chemotherapy and radiation have an important role in the palliative treatment of advanced NSCLC patients and should be included in BSC programs. Future randomized trials should assess the best way of combining these two approaches.

Adult↗
PubMed2001

Gemcitabine, cisplatin, and radiation in advanced, unresectable squamous cell carcinoma of the head and neck: a feasibility study.

Alternating chemoradiotherapy was shown by our institution to be superior to standard radiation in patients with nonsurgical squamous cell carcinoma of the head and neck (SCC-HN). Gemcitabine has shown in vitro and in vivo radiosensitizing properties, synergistic activity with cisplatin, and cytotoxic activity against SCC-HN. Thus, the authors tested the feasibility and antitumoral activity of a modified alternating chemoradiotherapy program that includes gemcitabine. Fourteen patients with stage IV (nine patients) or relapsed after surgery (five patients) unresectable SCC-HN were enrolled. None had previously received chemotherapy or radiotherapy. The treatment plan consisted of cisplatin, 20 mg/m2/day, days 1 to 5, weeks 1 and 5, and gemcitabine 800 mg/m2, day 5, weeks 1, 2, 3, and 5, 6, 7. Radiation was administered during weeks 2, 3, and 4 and 6, 7, and 8 with conventional fractionation up to 60 Gy. At the end of the combined therapy, patients had to receive two additional courses of cisplatin, 20 mg/m2/day, and fluorouracil, 200 mg/m2/day, for 5 days every 21 days. All the patients are evaluable for toxicity and 11 for response. Main grade III-IV toxicities and frequencies were: neutropenia (79%), neutropenia with fever (50%), thrombocytopenia (57%), anemia (35%), mucositis (100%), and cutaneous toxicity (14%). Ten patients (71%) had a weight loss greater than 10%. All but two patients needed hospitalization and tube feeding or parenteral nutrition. The median relative dose intensity of gemcitabine actually delivered was 83%. Two patients died 1 month after the end of treatment before the final evaluation. One patient died of sepsis during the additional cisplatin and fluorouracil courses before response assessment. Ten patients reached a complete response (intention to treat: 71%), and 1 patient had a partial response (9%). At a median follow-up of 34 months, the actuarial 3-year progression-free survival and overall survival are 41% and 63%, respectively. The estimated 3-year locoregional control is 70%. Considering the expected poor prognosis of the enrolled patients, this combined regimen showed an impressive antitumoral activity, but the severity of acute local and hematologic toxicity correlated makes the exportation of this regimen unproposable. However, the activity observed warrants the exploration of different, less toxic, chemo-radiotherapy programs including gemcitabine.

Aged↗
PubMed1998

5-Fluorouracil dose intensification and granulocyte-macrophage colony-stimulating factor in cisplatin-based chemotherapy for relapsed squamous cell carcinoma of the head and neck: a phase II study.

A previous phase I study showed that in a 5-day combination of cisplatin (CDDP) 20 mg/m2/day and 5-fluorouracil (5-FU) intravenous bolus, the maximum tolerable dose of 5-FU is 200 mg/m2/day without the use of growth factors and 300 mg/m2/day with recombinant human granulocyte-monocyte colony-stimulating factor (rhGM-CSF) support. In the present phase II study, 26 patients with relapsed and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) were treated with CDDP, 20 mg/m2/day, and 5-FU, 300 mg/m2/day intravenous bolus, for 5 consecutive days every 3 weeks. Granulocyte-macrophage colony-stimulating factor, 5 mg/kg/day subcutaneously, was administered from days 8 to 19. All patients had previously undergone surgery and/or radiation treatment. None had previously received chemotherapy. Mucositis (19% of the patients) and thrombocytopenia (42%) were the most frequent, but generally mild, toxicities. Relevant, GM-CSF-related side effects were detected in 12% of the patients. The median number of cycles delivered was four. Three complete and five partial responses were recorded (31% overall response rate). Further investigation of this regimen is unwarranted because of both its lack of improvement in antitumoral activity and the high costs incurred with the use of growth factors.

Adolescent↗
PubMed1997

Treatment with cisplatin and fluorouracil alternating with radiation favourably affects prognosis of inoperable squamous cell carcinoma of the head and neck: results of a multivariate analysis on 273 patients.

PURPOSE: The goal of the present analyses is to assess the association between different therapeutic approaches and both the probability of achieving a complete response and the risk of death in patients with stage III-IV, inoperable, squamous cell carcinoma of the head and neck (SCC-HN). PATIENTS AND METHODS: Between August 1983 and December 1990, 273 patients with stage III-IV, previously untreated, unresectable SCC of the oral cavity, pharynx and larynx, were included into two consecutive randomized multi-institutional trials (HN-7 and HN-8 protocols) coordinated by the National Institute for Cancer Research (NICR) of Genoa. The HN-7 protocol compared neo-adjuvant chemotherapy (four cycles of vinblastine, 6 mg/m2 i.v. followed by bleomycin, 30 IU i.m. six hours later, day 1; methotrexate, 200 mg i.v., day 2; leucovorin, 45 mg orally, day 3) (VBM) followed by standard radiotherapy (70-75 Gy in 7-8 weeks) (55 patients) to alternating chemoradiotherapy based on four cycles of the same chemotherapy alternated with three splits of radiation, 20 Gy each (61 patients). In the HN-8 protocol standard radiotherapy (77 patients) was compared to the same alternating program as the one used in the previous protocol but employing cisplatin, 20 mg/m2/day and fluorouracil, 200 mg/m2/day, bolus, both given for five consecutive days (CF) instead of VBM (80 patients). A single database was created with the patients on the two protocols. Age at diagnosis, gender, site of the primary tumor, size of the primary, nodal involvement, performance status and treatment approach were analyzed by the multiple logistic regression model and the Cox regression method. The analyses were repeated including the treating institutions as a covariate (coordinating center versus others). RESULTS: The multiple logistic regression analysis indicates that treatment (alternating more so than others, regardless of the chemotherapy regimen used) (P = 0.0001) is more likely to be associated with complete response. In addition, size of the primary tumor (P = 0.004), nodal involvement (P = 0.02) and performance status (P = 0.009) are prognostic variables affecting the probability of achieving a complete response. The Cox regression analysis indicates that treatment, performance status, size of the primary tumor, nodal involvement and, marginally, site of the primary tumor, are independent prognostic variables affecting the risk of death. When the radiation-alone therapy is adopted as the reference treatment, the relative risk of death is 0.58 (95% confidence interval (CI) 0.40-0.84) for alternating CF and radiation, 0.79 (95% CI 0.53-1.16) for alternating VBM and radiation and 1.30 (95% CI 0.89-1.92) for sequential VBM and radiation. When the treating institution is included in the model, a 34% increased risk of death (P = 0.04) is observed for patients treated outside the coordinating center. CONCLUSION: In our series of patients with advanced, unresectable SCC-HN, treatment with cisplatin and fluorouracil alternating with radiation was associated with a more favourable prognosis. The role of the treating institution in the modulation of the treatment outcomes was also relevant.

Adult↗
PubMed1997

Chemotherapy for relapsed head and neck cancer: paclitaxel, cisplatin, and 5-fluorouracil in chemotherapy-naive patients. A dose-finding study.

The aim of this trial was to identify the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) administered via a 3-hour infusion day 1, together with cisplatin 20 mg/m2/d days 1 to 3 and 5-fluorouracil 200 mg/m2/d bolus days 1 to 3 every 21 days. The prophylactic administration of colony-stimulating factors was not allowed. Twenty-three patients with relapsed and/or metastatic squamous cell carcinoma of the head and neck previously treated with surgery and/or radiotherapy were accrued. None had received chemotherapy previously. No grade 3/4 hematologic toxicity at nadir or other limiting toxicities were recorded with paclitaxel at 100 to 135 mg/m2 (six patients, 26 courses). Seven patients (six evaluable, 22 courses) were treated with 160 mg/m2. Grade 4 neutropenia at nadir with fever lasting 3 days was observed in one patient. Nonhematologic toxicities, including temporary peripheral neuropathy, asthenia, myalgias, vomiting, and mucositis were generally mild. Three patients were treated with 180 mg/m2 (eight courses). Grade 4 neutropenia at nadir was recorded in all patients and was febrile in two. Seven patients (six evaluable, 23 courses) were treated with paclitaxel 160 mg/m2, cisplatin 25 mg/m2/d, and 5-fluorouracil 250 mg/m2/d. Grade 4 febrile neutropenia at nadir was recorded in one patient. One episode of grade 4 mucositis and two episodes of grade 3 diarrhea were also recorded. Overall, eight responses (38%) were observed. In conclusion, the combination of paclitaxel 160 mg/m2, cisplatin 25 mg/m2/d, and 5-fluorouracil 250 mg/m2/d for 3 consecutive days can be administered safely without growth factor support. This regimen merits further investigation in a phase II trial.

Adult↗
PubMed1997

[Chemotherapy of head and neck carcinomas].

In most cases head and neck tumors manifest themselves on a local-regional level giving rise to highly mutilating pathologies with psycho-social repercussions. Surgery and radiotherapy are effective treatments for limited neoplasms (stage I-II). On the other hand, after surgery and/or radiotherapy, the treatment of locally advanced tumors (stage III-IV) or local recurrences and/or distant metastases is still problematic. For this reason chemotherapy, initially used only as a palliative, is today associated with other treatments to achieve better results both in terms of survival and disease-free time spans. Hence chemotherapy must be considered part of any multimodal primary treatment for advanced squamous cell carcinoma of the head and neck. In fact, numerous clinical studies have clearly demonstrated that adjuvant or neoadjuvant chemotherapy has a highly relative affect on survival in locally advanced diseases and that the incidence of distant metastases is reduced. This is not, however, followed by a similar reduction in local recurrences which are often the cause of death in such patients. It would, on the other hand, appear that survival is improved with integrated radio-chemotherapy. Immunochemotherapy, which has not as yet provided significant clinical results in cases of advanced tumors and/or metastases, must still be evaluated in the treatment of locally limited neoplasms. Organ preservation, which proves feasible in the larynx, leads one to hope it can be applied in other head and neck sites. The future balance leans in favor of the multidisciplinary approach and multi-center studies must be performed so that an adequate number of cases can be gathered over a brief period. This will make it possible to answer those questions and, at times, illusions which accompany chemotherapy in the treatment of advanced head and neck tumors.

Adult↗
PubMed1997

Chemoradiotherapy as an alternative to radiotherapy alone in fast proliferating head and neck squamous cell carcinomas.

The aim of this pilot study was to explore the prognostic relevance of cell kinetics parameters on the local control of patients affected by head and neck squamous cell carcinoma (HN-SCC), randomly assigned to receive either alternating chemoradiotherapy or partly accelerated radiotherapy. Between 1992 and 1995, 40 patients with HN-SCC at stages III and IV entered the study. Multiple primary tumor biopsies were obtained 6 h after in vivo infusion of bromodeoxyuridine, an analogue of thymidine that is incorporated in DNA-synthesizing cells. In vivo S-phase fraction labeling index (LI), duration of S-phase (TS), and potential doubling time (Tpot) were obtained by analysis of the flow cytometric content of bromodeoxyuridine and DNA. Twenty patients were treated by alternating chemotherapy and conventional radiotherapy (arm A), whereas 20 other matching patients received partly accelerated radiotherapy alone (arm B). Univariate local control analysis showed that LI, TS, and Tpot were not prognostically significant in either arm. However, local control probability at 2 years for fast growing tumors, characterized by a LI of 9%, was higher for patients treated with alternating chemoradiotherapy than it was for those treated with partly accelerated radiotherapy alone (68 versus 39%). Conversely, local control probabilities for slow proliferating tumors (LI, <9%) treated in the two arms were similar. These results suggest a potential role for alternating chemotherapy and radiotherapy in HN-SCC patients with fast growing tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Five-year update of a randomized trial of alternating radiotherapy and chemotherapy compared with radiotherapy alone in treatment of unresectable squamous cell carcinoma of the head and neck.

BACKGROUND: In 1992, we reported the first analysis of a randomized trial comparing alternating radiotherapy and chemotherapy with radiotherapy alone in the treatment of squamous cell carcinoma of the head and neck. The results of that 3-year analysis indicated that the combined treatment had superior efficacy. PURPOSE: After an additional 2 years of follow-up, we again compared the efficacy of the two treatment regimens, with attention paid to differences in overall survival, progression-free survival, and locoregional relapse-free survival. METHODS: One hundred fifty-seven patients with untreated, unresectable squamous cell carcinoma of the head and neck were randomly assigned to receive either chemotherapy (four courses of cisplatin [20 mg/m2] and fluorouracil [200 mg/m2], given daily for 5 consecutive days during weeks 1, 4, 7, and 10) plus radiotherapy (three courses of 20 Gy each, given in fractions of 2 Gy per day during weeks 2-3, 5-6, and 8-9) or radiotherapy alone (70 Gy total dose, given in fractions of 2 Gy per day, 5 days per week). Eighty patients received the combined therapy, and 77 were treated with radiotherapy alone. Responses, failures, and toxic effects associated with the two treatment regimens were compared. Overall survival, progression-free survival, and locoregional relapse-free survival were calculated according to the Kaplan-Meier method; the logrank test was used to compare survival parameters between the two patient groups. Reported P values are two-sided. RESULTS: As reported previously, toxic effects associated with the combined therapy included both chemotherapy- and radiotherapy-related effects; however, the incidence and severity of mucositis were nearly identical among patients in the two treatment arms. The combined treatment was associated with a statistically significant increase in the frequency of complete response (i.e., the disappearance of clinically detectable disease for at least 4 weeks) (43% for the combined-treatment group compared with 22% for the radiotherapy-only group; P = .037, chi-squared test). Five-year estimates of overall survival in the combined-treatment group compared with the radiotherapy-only group were 24% (95% confidence interval [CI] = 14%-40%) and 10% (95% CI = 4%-24%), respectively (P = .01, logrank test). The estimates of progression-free survival at 5 years in the combined-treatment group compared with the radiotherapy-only group were 21% (95% CI = 11%-37%) and 9% (95% CI = 3%-22%), respectively (P = .008, logrank test). Finally, the 5-year estimates of locoregional relapse-free survival were 64% (95% CI = 36%-84%) in the combined-treatment group and 32% (95% CI = 10%-65%) in the radiotherapy-only group (P = .038, logrank test). CONCLUSIONS AND IMPLICATIONS: The superiority of alternating chemotherapy and radiotherapy over radiotherapy alone in treating unresectable squamous cell carcinoma of the head and neck seen at 3 years was confirmed at 5 years. However, additional trials must be conducted before considering the combined approach as standard therapy.

Antimetabolites, Antineoplastic↗
PubMed1994

Randomised phase II study of methotrexate (MTX) versus methotrexate plus lonidamine (MTX + LND) in recurrent and/or metastatic carcinoma of the head and neck.

Between March 1990 and March 1992, 89 patients with recurrent and/or metastatic squamous cell cancer of the head and neck were randomised to receive either intravenous methotrexate (MTX) at a weekly dose of 40 mg/m2 plus lonidamine (LND) given orally at a starting dose of 75 mg three times daily for 3 days and then at a dose of 150 mg three times daily (arm MTX + LND) or methotrexate alone (arm MTX) at the same doses as arm MTX + LND. Complete remissions were observed in 10.5% of the patients in arm MTX + LND, and partial remissions in another 15.8%, yielding a 26.3% response rate. In arm MTX, only partial remissions were observed, yielding an overall response rate of 18.2%. Haematological toxicity was mild in both groups. Mild testicular pain (21%) and myalgias (31%) occurred only in patients treated with LND.

Adult↗
PubMed1994

Chemotherapy in head and neck cancer.

Chemotherapy has been used for many years as a palliative approach to advanced squamous cell carcinoma of the head and neck. Regimens employed have slowly evolved during this time, and the combination of cisplatin and 5-fluorouracil is still standard chemotherapy for such a tumour. However, clinical approaches to advanced squamous cell carcinoma of the head and neck are changing dramatically as physicians become increasingly familiar with multidisciplinary treatments. Integrating chemotherapy and radiotherapy, neo-adjuvant or adjuvant treatments and organ preservation are stimulating fields of investigation involving chemotherapy which definitely warrant further investigation.

Carcinoma, Squamous Cell↗
PubMed1994

Intensified chemotherapy with granulocyte-monocyte colony stimulating factor protection in advanced, relapsed squamous cell carcinoma of the head and neck. A phase I study.

BACKGROUND: The administration of granulocyte-monocyte colony stimulating factor (GM-CSF) should allow an increase in the doses of chemotherapy for patients with advanced cancers of the head and neck. PATIENTS AND METHODS: Eleven patients with histologically proven relapsed squamous cell carcinoma of the head and neck entered this Phase I study based on the combination of cisplatin (20 mg/m2/day for 5 days), escalating doses of 5-fluorouracil, both given by intravenous injection from day 1 to 5, and GM-CSF, 5 micrograms/kg from day 8 to day 19. RESULTS: The maximum tolerated 5-fluorouracil dosage was 300 mg/m2 i.v. bolus for 5 consecutive days q. 3 weeks. Thrombocytopenia was the limiting factor to further increase of 5-fluorouracil dosage. Moderate to severe stomatitis were quite rare despite the increased dose of the antimetabolite. GM-CSF was well tolerated: no significant local or systemic side effects attributable to this drug were recorded. CONCLUSIONS: Adding GM-CSF to the combination of cisplatin and 5-fluorouracil allowed to increase 5-fluorouracil dose up to 50% over the conventional dosage. Further increase of the dose was precluded by the development of severe thrombocytopenia.

Aged↗