Phase II study of cisplatin preceding gemcitabine in patients with advanced oesophageal cancer.

BACKGROUND: For oesophageal cancer there is no effective standard therapy. We studied the feasibility and efficacy of the cisplatin-gemcitabine combination chemotherapy in patients with unresectable oesophageal cancer. PATIENTS AND METHODS: Thirty-six chemona?ve patients with unresectable or metastatic oesophageal adenocarcinoma (24) or squamous-cell-carcinoma (12) were treated with cisplatin (50 mg/m2, days 1 and 8), followed by gemcitabine (800 mg/m2, days 2, 9 and 16), every 28 days. Feasibility and efficacy were studied. RESULTS: Toxicity was substantial but manageable. A median number of four therapy cycles was given. The most frequent grade > or = 3 toxicities were leukopenia (75%) and neutropenia (83%). Three patients developed neutropenic fever. Grade 3/4 thrombocytopenia occurred in 24 out of 36 patients (67%), but did not result in serious bleeding disorders. Myelotoxicity was cumulative and required omission of gemcitabine on day 16 in 63% of cycles. Anaemia required treatment with erythropoietin, red blood cells or both in 81% of patients. Non-haematological toxicity consisted mainly of grade 1/2 nausea/vomiting or fatigue. Fourteen out of 34 evaluable patients had a major objective response (41%; two complete and 12 partial responses). The median actuarial survival was 9.8 months. CONCLUSION: This cisplatin-gemcitabine regimen was feasible, with myelosupression being the main toxicity, and had significant activity in patients with advanced oesophageal cancer.     

A phase II trial of gemcitabine, 5-fluorouracil and leucovorin in advanced esophageal carcinoma

BACKGROUND: The aim of this study was to evaluate the overall response rate, toxicity and overall survival in patients with locally advanced or metastatic esophageal cancer treated with gemcitabine, 5-fluorouracil (5-FU) and leucovorin. PATIENTS AND METHODS: Patients with either adenocarcinoma or squamous cell carcinoma of the esophagus could enroll; however, patients could not have received prior chemotherapy for metastatic disease. Treatment cycles consisted of infusions of all three agents at days 1, 8 and 15, repeated every 28 days. Patients received gemcitabine 1,000, leucovorin 25 and 5-FU 600 mg/m(2). Tumor assessment was performed every 2 cycles. Responses were assessed using the Eastern Cooperative Oncology Group solid tumor response criteria. RESULTS: Thirty-five patients with metastatic or locally advanced esophageal cancer enrolled. One complete response and ten partial responses were observed for an overall response rate of 31.4%. An additional 11 patients had stable disease as their best response. The median survival was 9.8 months with a 1-year survival rate of 37.1%. Toxicity was predominately hematologic, with 58% of patients experiencing grade 3 or 4 neutropenia. CONCLUSION: The combination of gemcitabine, 5-FU and leucovorin had activity in advanced esophageal cancer. Patients tolerated the regimen well, with myelosuppression occurring most commonly. The combination merits further investigation as a treatment for esophageal cancer.     

Phase II trial of cisplatin and gemcitabine in advanced squamous-cell carcinoma of the head and neck

Background: To evaluate the toxicity profile and efficacy of cisplatin combined with gemcitabine in patients with irresectable locally recurrent or metastatic squamous cell carcinoma of the head and neck.Patients and methods: Gemcitabine was given at a dose of 800 mg/m2 on days 1, 8 and 15, plus cisplatin at a dose of 50 mg/m2 on days 1 and 8; every four weeks.Results: Twenty-four patients with a median age of 59 years (range 42–74) were included. All patients were evaluable for toxicity and 22 patients were assessable for response. Eleven cases had advanced recurrent locoregional disease while 13 patients had metastatic disease. One CR (4.7%) and four PR (18%) were observed, for an overall response rate of 22.7% (95% CI: 8%–42%). The main toxicity was hematological: neutropenia grade 3–4 in 28% of the cycles and thrombocytopenia grade 3–4 in 16%. The most significant non-hematological toxicity was asthenia grade 2–3 in 24% of the cycles.Conclusions: This cisplatin plus gemcitabine combination schedule has a favourable toxicity profile with a discrete activity in patients with locally recurrent or metastatic squamous-cell carcinoma of the head and neck.     

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

PURPOSE: This phase II study was undertaken to determine the efficacy of adding infusional fluorouracil (FU) to the chemotherapy doublet of gemcitabine and cisplatin in patients with advanced pancreatic cancer. PATIENTS AND METHODS: The eligibility criteria included histologically or cytologically confirmed adenocarcinoma of the pancreas that was either unresectable or metastatic. No prior gemcitabine therapy was allowed. Patients received a combination of gemcitabine 1000 mg/m2 intravenously (IV) on days 1, 8, and 15; cisplatin 50 mg/m2 IV on days 1 and 15; and FU 175 mg/m2/d from days 1 to 15 by continuous IV infusion. Cycles were repeated every 28 days. Objective tumor response and toxicity were evaluated according to the World Health Organization criteria. RESULTS: A total of 47 patients (median age, 57 years; males, 59%) were enrolled. Sixteen patients had locally advanced (LA) disease, and 31 patients had metastatic disease. A total of 183 cycles of chemotherapy were administered. In patients with metastatic disease (n = 31), the probability of survival at 6 and 12 months was 66% and 34%, respectively. Objective partial response or stable disease was observed in 26% (90% confidence interval [CI], 0.14 to 0.41) and 61% (90% CI, 0.45 to 0.74) of patients, respectively. In patients with LA disease (n = 16), there were three partial responses (19%; 90 CI, 0.07 to 0.39). One patient in this group was successfully resected after FU-based radiotherapy. The most common grade 3 to 4 toxicities were neutropenia (60%), thrombocytopenia (42%), and anemia (26%). Thirteen patients were hospitalized for treatment-related complications. CONCLUSION: The combination of gemcitabine, cisplatin, and infusional FU has significant activity in patients with advanced pancreatic cancer.     

A phase II study of epirubicin, cisplatin and capecitabine combination chemotherapy in patients with metastatic or advanced gastric cancer

OBJECTIVES: The purpose of this study was to evaluate the antitumor activity and safety of an epirubicin, cisplatin, and capecitabine (ECX) combination in patients with metastatic or advanced gastric cancer. PATIENTS AND METHODS: Patients with metastatic or advanced measurable gastric adenocarcinoma received ECX combination chemotherapy. Epirubicin 50 mg/m2 and cisplatin 60 mg/m2 were administered on day 1 by intravenous injection. Capecitabine 1,000 mg/m2 twice daily was administered orally on day 1-14. The cycle was repeated every 3 weeks. RESULTS: Fifty-four patients were enrolled in this study. Fifty patients were assessable for responses and 53 for toxicity. A total of 250 cycles were administered. The overall best response rate by intent-to-treat analysis was 59% including 52% partial responses and 7% complete responses. Median response duration and time to progression was 5.8 and 6 months, respectively. Median survival for all patients was 9.6 months (95% CI, 8.7-10.5 months). The most common grade 3/4 hematological adverse event was neutropenia in 31% (76 cycles) including febrile neutropenia in 4.8% (11 cycles). Non-hematological toxicity was generally mild and reversible. Grade 3/4 nausea, vomiting and stomatitis occurred in 8, 9, and 8% of the patients, respectively. Hand-foot skin reactions developed in 51% of patients, but most were self-limited. Grade 3 occurred in only 4%. One patient died of neutropenic sepsis. CONCLUSIONS: ECX combination regimen showed high anti-tumor activity with a tolerable toxicity pattern as a front-line chemotherapy for patients with metastatic or advanced gastric cancer.     

Gemcitabine combined with oxaliplatin in advanced pancreatic adenocarcinoma: final results of a GERCOR multicenter phase II study.

PURPOSE: Based on preclinical in vitro synergy data, this study evaluated the activity and toxicity of a gemcitabine/oxaliplatin combination in patients with metastatic and locally advanced pancreatic adenocarcinoma. PATIENTS AND METHODS: Previously untreated metastatic and locally advanced unresectable pancreatic adenocarcinoma patients were enrolled onto this multicenter phase II study. Patients received gemcitabine 1,000 mg/m(2) as a 10-mg/m(2)/min infusion on day 1 and oxaliplatin 100 mg/m(2) as a 2-hour infusion on day 2 every 2 weeks. Patients with metastatic disease were treated until evidence of progressive disease, whereas patients with locally advanced disease received six cycles in the absence of progression, followed when appropriate by concomitant radiochemotherapy. RESULTS: Among 64 eligible patients included in eight centers, 30 had locally advanced and 34 had metastatic disease. Response rate for the 62 patients with measurable disease was 30.6% (95% confidence interval, 19.7% to 42.3%), 31.0% for locally advanced and 30.3% for metastatic patients. Among 58 assessable patients, 40% had clinical benefit. Median progression-free survival and median overall survival (OS) were 5.3 and 9.2 months, respectively, with 36% of patients alive at 1 year. Median OS for patients with metastatic disease and locally advanced disease were 8.7 and 11.5 months, respectively. With 574 treatment cycles (median per patient, nine; range, zero to 27), grade 3/4 toxicity per patient was 11% for neutropenia and thrombocytopenia, 14% for nausea or vomiting, 6.2% for diarrhea, and 11% for peripheral neuropathy, with no toxic deaths. CONCLUSION: Palliative effects, response rate, and survival observed with this well-tolerated gemcitabine/oxaliplatin combination deserve additional evaluation. A comparative study of combination therapy versus gemcitabine alone is ongoing.     

A phase II trial of the combination of gemcitabine, ifosfamide and cisplatin in the treatment of advanced non-small cell lung cancer

OBJECTIVE: This phase II trial was designed to assess the efficacy and toxicity profile of the combination of gemcitabine, ifosfamide and cisplatin (GIP) in the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients included in the study were those with surgically unresectable or metastatic NSCLC, with bidimensionally measurable disease, a Karnofsky performance status > 60, and who had not received previous chemotherapy. Treatment consisted of 1000 mg/m(2) gemcitabine on days 1 and 8, 3 g/m(2) ifosfamide on day 1, and 50 mg/m(2) cisplatin on day 1, administered in 21-day cycles. A maximum of six cycles were administered. RESULTS: Between March 1996 and December 1997, 60 patients were included in the study (37 stage III and 23 stage IV), of which 59 were evaluated for response. An objective response was obtained in 43% of patients (3% complete and 40% partial responses), whereas 22% had stable disease. The median survival time for the whole group was 52 weeks (65 weeks in patients with stage III, and 35 weeks in stage IV). The most frequent toxicity was haematological, 56% of patients presented grade 3 or 4 myelotoxicity in one of the cycles, although only seven episodes of febrile neutropenia were recorded in the 255 cycles administered. CONCLUSIONS: The GIP regimen attains response rates similar to those obtained with the gemcitabine plus cisplatin combination used in advanced NSCLC, and had an acceptable toxicity profile.     

吉西他滨联合顺铂治疗晚期非小细胞肺癌临床研究

目的：观察吉西他滨联合顺铂治疗晚期非小细胞肺癌的疗效及毒副反应。方法：经病理组织学或细胞学证实的43例晚期非小细胞肺癌患者给予吉西他滨1000mg/m2静滴,第1,8,15天,顺铂30mg/m2静滴,第1－3天,28天为一周期,或吉西他滨1200mg/m2静滴,第1,8天,顺铂30mg/m2静滴,第1－3天,21天为一周期,结果：全组CR1例,PR20例,SD13例,PD9例,总有效率48．8％,初治病例有效率为62．5％,复治病例为31．6％,两组间差异具有显著性（P＜0．05）,毒副反应以白细胞及血小板下降为常见,但均可耐受,结论：吉西他滨联合顺铂治疗晚期非小细胞肺癌具有较好的疗效。毒性可以耐受。     

健择合并顺铂治疗晚期复治恶性肿瘤25例报告

目的 探讨健择合并顺铂对复治的局部晚期复发或转移性恶性肿瘤的疗效和毒性反应。方法 使用健择（1000mg/m^2,iv,第1、8、15天）加顺铂（50mg,iv,第15－17天）联合化疗两个周期（28天为一个周期）,治疗25例复治的晚期复发或转移恶性肿瘤患者。结果 可评价的患者20例,无CR患者,PR5例（25％）、NC9例（45％）,PD6例（30％）,总缓解率25％。本研究主要毒性反应为轻到中度骨髓抑制,其它毒副反应少见。结率 健择合并顺铂对复治的部分晚期恶性肿瘤有一定疗效,毒性反应可以耐受,可在临床推广使用。     

Single-agent gemcitabine: an active and better tolerated alternative to standard cisplatin-based chemotherapy in locally advanced or metastatic non-small cell lung cancer

This randomized study was designed to determine the response rates, survival and toxicities of single-agent gemcitabine (GEMZAR) and a combination of cisplatin/etoposide in chemonaive patients with non-resectable, locally advanced or metastatic non-small cell lung cancer (NSCLC). Gemcitabine 1000 mg/m2 was given as a 30-min intravenous infusion on days 1, 8, 15 of a 28-day cycle, cisplatin 100 mg/m2 on day 1, and etoposide 100 mg/m2 on days 1 (following cisplatin), 2 and 3. Major eligibility criteria included histologically confirmed non-small cell lung cancer, measurable disease, Zubrod performance status 0-2, no prior chemotherapy, no prior radiation of the measured lesion, and no CNS metastases. One hundred and forty-seven patients were enrolled, 72 in the gemcitabine and 75 in the cisplatin/etoposide arm. Patient characteristics were well-matched across both arms. Sixty-seven gemcitabine and 72 cisplatin/etoposide patients were qualified for efficacy analysis. There were no complete responses, but 12 partial responses in the gemcitabine arm and 11 in the cisplatin/etoposide arm, for protocol-qualified response but 12 partial responses in the gemcitabine arm and 11 in the cisplatin/etoposide arm, for protocol-qualified response rates of 17.9% (95%, CI: 9.6-29.2%,) and 15.3% (95% CI: 7.9-25.7%,), respectively. Median survival times were 6.6 months (95% CI: 4.9-7.3 months) for gemcitabine and 7.6 months (95% CI: 5.4-9.3 months) for cisplatin/etoposide. The 1-year survival probability estimate was 26% for gemcitabine and 24% for cisplatin/etoposide. There were no statistically significant between-group differences in time-to-event measures, but patients in the gemcitabine arm had a greater probability of achieving a tumour response after 2 months (probability estimate: 8 vs. 0%,) and of the response lasting at least 6 months (73 vs. 45%,). Clinical and haematologic toxicity was more pronounced in the cisplatin/etoposide arm. Quality-of-life measures indicated a significant worsening of symptomatology in the cisplatin/etoposide arm for hair loss, nausea and vomiting, and appetite loss. This randomized study provides further evidence that single-agent gemcitabine is an active and effective therapy for patients with non-resectable. locally advanced or metastatic NSCLC and good performance status, and that it is better tolerated than the combination cisplatin/ etoposide.     

吉西他滨联合奥沙利铂治疗进展期胰腺癌（附40例）

目的：观察吉西他滨（择菲GEM）联合奥沙利铂（艾恒OXA）组成的GEMOX方案治疗进展期胰腺癌的有效性和安全性。方法：进展期胰腺癌40例,应用GEM800mg／m2静滴半小时,d1,d3;OXA60mg／m2静滴2小时,d2,d9;21天重复。至少接受2个周期的化疗,按照WHO标准进行评价。结果：观察化疗后肿瘤原发病灶的变化情况及化疗的不良反应。临床有效率为17．5％,具有较好的耐受性,不良反应主要有骨髓抑制和消化系统反应。结论：健择联合艾恒治疗进展期胰腺癌疗效较好,不良反应可以耐受。     

Docetaxel and cisplatin: An active regimen in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck

Background: Docetaxel and cisplatin are among the most active antitumor agents in head and neck cancer, and phase I studies found the combination of the two drugs to be feasible. The EORTC ECSG performed a multicenter phase II study in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck to evaluate the antitumor efficacy and toxicity of this combination.Patients and methods: Eligibility criteria included written informed consent, a WHO performance status <2, life expectancy of >12 weeks, and adequate bone marrow, liver and renal function. Neoadjuvant pretreatment with cisplatin-based chemotherapy or prior radiotherapy were allowed. Patients were ineligible if pretreated with taxoids, had CNS involvement, concurrent malignancy, peripheral neuropathy, or no measurable disease. Treatment consisted of docetaxel 100 mg/m2 (one-hour i.v. infusion), followed by cisplatin 75 mg/m2 (three-hour i.v. infusion), repeated every three weeks. Supportive care included hydration, 5HT3- antagonists, and corticosteroids.Results: Forty-four patients (median age 55 years, range 35–76) entered the trial; 41 patients were eligible, 164 cycles of treatment were evaluable for toxicity, and 31 patients for response. Fourteen patients had undergone prior surgery, 15 had received radiotherapy, and five had had chemotherapy. A median number of four treatment cycles (range 1–6) was given. Hematologic and non-hematologic toxicities were common, but hypersensitivity reactions and fluid retention were very infrequent due to corticosteroid prophylaxis. Four patients were taken off the study due to toxicity, and one toxic death occurred due to pneumonia. Among 41 eligible patients, objective responses as confirmed by independent review included six complete remissions and 16 partial remissions, resulting in an overall response rate of 53.7% (95% confidence interval: 37.4%–69.3%). Responses occurred in locally advanced, recurrent and metastatic disease, both in pre- and non-pretreated patients. Of 22 evaluable, non-pretreated patients with locally advanced or metastatic disease, five achieved complete responses, and 14 partial responses. Observed among nine evaluable pretreated patients with locally advanced or metastatic head and neck cancer were one complete response and two partial responses.Conclusion: The combination of docetaxel and cisplatin is feasible and active in locally advanced, recurrent, and metastatic squamous cell carcinoma of the head and neck.     

A multicenter phase II study of sequential vinorelbine and cisplatin followed by docetaxel and gemcitabine in patients with advanced non-small cell lung cancer

PURPOSE: To evaluate the activity and toxicity of the sequential administration of vinorelbine/cisplatin (VC regimen) followed by the docetaxel/gemcitabine (DG regimen) combination in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND TREATMENT: Fifty-nine previously untreated patients with advanced/metastatic NSCLC received three cycles of cisplatin 80 mg/m(2) (day 1), and vinorelbine 30 mg/m(2) (days 1 and 8 every 3 weeks; VC regimen), followed by six cycles of docetaxel (65 mg/m(2), day 1) and gemcitabine (1,500 mg/m(2), day 1), (DG regimen) every 2 weeks. RESULTS: One (1.7%) complete and 26 (44.1%) partial responses were achieved for an overall response rate of 45.8% (95% CI 33.05-58.48%); 12 (20.3%) patients had stable disease and 20 (33.9%) progressive disease. The median time to progression was 5.3 months, the median survival time 12.5 months and the 1-year survival rate 51%. The main toxicity was grade III/IV neutropenia occurring in 25.5% of patients; all other hematologic and non-hematologic toxicities were relatively infrequent. CONCLUSIONS: The sequential administration of VC and DG regimens was well tolerated and active against advanced NSCLC and merits to be further evaluated against a single doublet.     

Phase II study of combination chemotherapy with gemcitabine and cisplatin for patients with metastatic pancreatic cancer

OBJECTIVE: The objectives of this study were to evaluate the efficacy and toxicity of combination chemotherapy with gemcitabine and cisplatin in patients with metastatic pancreatic cancer. METHODS: Patients na?ve to chemotherapy who had histologically or cytologically confirmed metastatic pancreatic adenocarcinoma were entered. Gemcitabine was given at a dose of 1000 mg/m2 over 30 min on days 1, 8 and 15, and cisplatin was given at a dose of 80 mg/m2 over 150 min on day 1, in 28-day cycles. RESULTS: A total of 38 patients were enrolled in this study between August 2001 and December 2003. There were no complete responses and 10 partial responses, resulting in an overall response rate of 26% (95% CI: 13.4-43.1%]. Twenty-one patients (55%) had stable disease, whereas 7 (18%) had progressive disease. The median time to progression was 4.2 months and the median overall survival was 7.5 months with a 1-year survival rate of 24%. Grade 3-4 toxicities included neutropenia in 26 patients (68%), thrombocytopenia in 19 (50%), anorexia in 15 (39%) and nausea in nine (24%). There was only one episode of neutropenic fever and there were no significant bleeding episodes or treatment-related deaths. CONCLUSION: The combination of gemcitabine and cisplatin administered by this schedule produced a good response rate associated with moderate but manageable toxicities in patients with metastatic pancreatic cancer.     

Modified Docetaxel and Cisplatin in Combination with Capecitabine (DCX) as a First-Line Treatment in HER2-Negative Advanced Gastric Cancer

Background: Docetaxel and cisplatin in combination with fluorouracil (DCF) regimen is accepted to be oneof the standard regimens in the treatment of advanced gastric cancer. However, substantial toxicity has limitedits use in daily clinical practice. Therefore, modification of DCF regimens, including introduction of capecitabinehas been investigated to improve the safety profiles. In the present study, the efficacy and toxicity of a regimenwith a modified dose of docetaxel and cisplatin in combination with oral capecitabine (DCX) was evaluated inuntreated patients with HER2-negative advanced gastric cancer. Materials and Methods: Fifty-four patientswith HER2-negative locally advanced or metastatic gastric cancer were included in this cohort. Patients receiveddocetaxel 60 mg/m2 plus cisplatin 60 mg/m2 (day 1) combined with capecitabine 1650 mg/m2 (days 1–14) every3 weeks. Treatment response, survival, and toxicity were retrospectively analyzed. Results: The median age was54 years (range: 24–76). The majority of patients (70%) had metastatic disease, while 11 patients (21%) hadrecurrent disease and underwent curative gastrectomy, and 5 patients (9%) had locally advanced disease (LAD).The median number of DCX cycles was 4. There were 28 partial responses and 11 complete responses, with anoverall response rate of 72%. Curative surgery could be performed in four patients among five with LAD. Atthe median follow-up of 10 months, the median progression-free survival (PFS) and overall survival (OS) of theentire cohort of patients were 7.4 and 12.1 months, respectively. Dose modification was done in 12 patients dueto toxicity in 8 and noncompliance in 4 patients. The most common hematological toxicity was neutropenia,which occurred at grade 3-4 intensity in 10 of 54 patients (27.7%). Febrile neutropenia was diagnosed only intwo cases. Conclusions: DCX regimen offers prominent anti-tumor activity and considered to be effective firstlinetreatment with manageable toxicity for patients with HER2-negative advanced gastric cancer.     

Phase II study of a fixed dose-rate infusion of gemcitabine associated with uracil/tegafur in advanced carcinoma of the pancreas.

BACKGROUND: The objectives of this study were to evaluate the efficacy and toxicity of a fixed dose-rate infusion of gemcitabine associated with uracil/tegafur (UFT) in patients with advanced adenocarcinoma of the pancreas. PATIENTS AND METHODS: Forty-three chemotherapy-na?ve patients with adenocarcinoma of the pancreas were included in this phase II study. All of whom had a Karnofsky performance status >or=50 and bi-dimensionally measurable disease (either advanced non-resectable or metastatic); median age 59 years (range 39-77); male:female ratio 29:14. Eight patients (19%) had locally advanced disease and 35 (81%) distant metastases. Treatment consisted of gemcitabine 1200 mg/m(2) given as a 120-min infusion weekly for 3 consecutive weeks, plus oral UFT 400 mg/m(2)/day (in 2-3 doses per day) on days 1-21, cycles were given every 28 days. Measurements of efficacy included response rate, clinical benefit response, time to disease progression and overall survival. RESULTS: A total of 192 cycles of chemotherapy were delivered with a median of four per patient. There were two complete responses (5%) and 12 partial responses (28%), producing an overall response rate of 33% [95% confidence interval (CI) 16% to 49%]. Thirteen patients (30%) had stable disease, whereas 16 (37%) had a progression. The median time to progression was 6 months and the median overall survival was 11 months. Twenty-five patients (64%, 95% CI 47% to 78%) experienced a clinical benefit response. Grade 3-4 WHO toxicities were: neutropenia in nine patients (21%); thrombocytopenia in four (9%); anaemia in five (12%); diarrhoea in four (9%); and asthenia in one (2%). CONCLUSIONS: A fixed dose-rate infusion of gemcitabine associated with UFT was well tolerated and showed promising activity in patients with locally advanced or metastatic carcinoma of the pancreas. This is an appropriate palliative treatment in this setting.     

Optimisation of 5-fluorouracil (5-FU)/cisplatin combination chemotherapy with a new schedule of hydroxyurea, leucovorin, 5-FU and cisplatin (HLFP regimen) for metastatic oesophageal cancer

To improve the efficacy and tolerance of the 5-fluorouracil (5-FU)/cisplatin combination in metastatic esophageal cancer, we designed a new therapeutic schedule, the HLFP regimen. 42 patients with metastatic oesophageal adenocarcinoma (n=10) or squamous cell carcinoma (n=32) were prospectively enrolled in the study. All had bidimensionally measurable disease. The HLFP regimen consisted of twice-monthly oral administration of hydroxyurea 1 g/m(2) on days 0, 1 and 2; a 2-h infusion of leucovorin 200 mg/m(2) and a bolus of 5-FU 400 mg/m(2) followed by a 22-h infusion of 5-FU 600 mg/m(2) on days 1 and 2; and, every two cycles, 80 mg/m(2) cisplatin on day 3. Relief of dysphagia and other symptoms were monitored, together with body weight changes. Major objective responses were observed in 24 patients (57%, 95% Confidence Interval (CI): 42-72%), including four complete responses (10%). The median progression-free survival and overall survival times were 8 and 12.7 months, respectively. Weight gain was observed in 48% of patients, and dysphagia improved in 76%. Grade 3-4 toxicity occurred in 40% of patients, with grade 4 neutropenia in 12% and grade 3 thrombocytopenia, vomiting and diarrhoea in 7-9% of patients. There were no treatment-related deaths. These results suggest that the HLFP regimen is an active and well-tolerated chemotherapy for metastatic oesophageal carcinoma.     

Gemcitabine plus cisplatin (GC): a salvage regimen for advanced breast cancer patients who have failed anthracycline and/or taxane therapy

BACKGROUND: In clinical studies of both heavily and minimally pretreated patients with advanced breast cancer, the combination of Gemcitabine plus cisplatin (GC), given in a variety of schedules and doses, has demonstrated moderate safety and efficacy in both heavily and minimally pretreated advanced breast cancer with response rate from 29-63% (median 46%). METHODS: We evaluated the activity and toxicity of another GC regimen (gemcitabine 1,000 mg/m(2) days 1, 8 plus cisplatin 75 mg/m(2) day 1 every 3 weeks) in 30 breast cancer patients who failed chemotherapy with anthracycline and/or taxanes as adjuvant or neoadjuvant, or primary therapy. RESULTS: We obtained overall response in 15 of 29 evaluable patients (52%), with responses occurring in all subgroups of disease (unresectable locally advanced, locoregional recurrence, and distant metastasis). Toxicity was primarily hematologic, with grade 3/4 neutropenia and thrombocytopenia in 37% and 17% of patients, respectively. The only grade 3/4 non-hematologic toxicity was grade 3 nausea/vomiting in 12% of patients. CONCLUSION: Our data suggest that gemcitabine plus cisplatin appears to be effective and has an acceptable toxicity profile in anthracycline and/or taxane pretreated patients with advanced breast cancer.     

A new cisplatin/gemcitabine schedule in locally advanced (IIIB) and metastatic (IV) non-small cell lung cancer: relationship between dose-intensity and efficacy. A phase II study

BACKGROUND: Cisplatin/gemcitabine are one of the "standard" chemotherapy schedules in locally advanced and metastatic NSCLC cancer. A number of trials documented that omission of gemcitabine on day 15 and reduction of cisplatin up to 70 mg/mq are equivalent in term of response rates to "classic" administrations on days 1, 8 and 15 with cisplatin 100 mg/mq. The aim of this study was to confirm this evidence and to demonstrate that a further reduction of gemcitabine dose-intensity may be performed with the same efficacy on response. PATIENTS AND METHODS: Fifty untreated patients with locally advanced and metastatic NSCLC entered the study: 24 stage IIIB and 26 stage IV. The median age was 65 years (range 32-76); 44 males and 6 females Genicitabine was administered 1000 mg/mq weekly on days 1 and 8 followed by a 2-week rest and cisplatin 80 mg/mq on day 2 of each 28-day-cycle. RESULTS: Forty-five patients were evaluable for response and all for toxicity. The overall response rates were 35.5% with 16 partial responses (95% Confidence Interval: 32%-61%). Most of the objective responses were seen in IIIB patients (56% of the stage IIIB and 44% of the stage IV patients responded). According to the intent-to-treat-principle, the response rates were 32% (16 out of 50 patients). The median dose-intensity of gemcitabine and cisplatin was respectively 477.6 mg/mq/week (481.4 for responders) and 19.5 mg/mq/week (19.9 mg/mq for responders). The median response duration was 5 months (range 1-18) and the median time to progression was 5 months (1-21); median survival was 9 months (range 2-31). The main toxicity was haematological: thrombocytopenia grade IV in 5 patients (10%) and grade III in 11 patients (22%); neutropenia grade III-IV in 4 patients (8%); grade III anemia in 3 (6%). Asthenia was the most significant non-haematological toxicity and was observed in 19 patients (38%). CONCLUSION: This trial confirmed the efficacy of a schedule with 2 administrations of gemcitabine (on days 1, 8) and a cisplatin dose on day 2 lower than 100 mg/mq. Moreover, the same efficacy was obtained with a median-dose intensity of cisplatin and gemcitabine lower than planned in a 21-day-schedule. For safety and low toxicity, we think that this schedule provides another chance to treat patients with non-small cell lung cancer, especially the elderly or patients with coexistent medical illnesses.     

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.