Gemcitabine in soft tissue or bone sarcoma resistant to standard chemotherapy: a phase II study

Purpose: To assess the efficacy of gemcitabine in patients with a variety of sarcomas that have failed to respond or escaped Adriamycin- and ifosfamide-based chemotherapy. Patients and methods: A group of 18 symptomatic heavily pretreated patients with sarcomas of bone or soft tissue received one induction course of gemcitabine at a dose of 1000 mg/m² per week for 7 consecutive weeks, followed by 1 week rest. Response to the induction course was assessed by interview and by repeated ancillary tests. If no progression was observed, maintenance by gemcitabine 1000 mg/m² per week for 3 weeks every 28 days was given until failure was clinically or radiologically evident. Results: A total of 51 cycles of gemcitabine were given including 18 cycles of induction. A mean of 3.6 postinduction cycles were given to nine patients. The treatment was well tolerated by the patients. One partial response (leiomyosarcoma) and one minimal response (angiosarcoma) were observed, yielding a true objective response rate of 5.5%. An additional six patients achieved stabilization of disease (chondrosarcoma and osteosarcoma), yielding an overall progression-free rate of 44%. The median time to progression was more than 27 weeks. Clinical benefit response was observed only in those who also achieved a progression-free state. Conclusion: Gemcitabine was found to be effective in achieving stabilization and even a minimal response of soft tissue or bone sarcoma refractory to standard chemotherapy. Received: 10 June 1999 / Accepted: 7 September 1999     

Efficacy and safety of gemcitabine monotherapy in patients with transitional cell carcinoma after Cisplatin-containing therapy: a Japanese experience

BACKGROUND: In Japan, the standard chemotherapy for advanced transitional cell carcinoma (TCC) of the urothelium is MVAC (methotrexate, vinblastine, adriamycin, cisplatin). However, a second-line therapy is still required for patients with recurrent TCC who discontinued MVAC because of toxicity or have MVAC refractory tumors. METHODS: We evaluated gemcitabine monotherapy in patients with advanced TCC who were previously treated with a platinum-based regimen. Gemcitabine (1000 mg/m2) was given once a week for three consecutive weeks followed by a week of rest. This cycle was repeated at least three times, or until disease progression or intolerable adverse events were observed. RESULTS: Of the 46 patients entered into this study, 44 received gemcitabine. Performance status (PS) at study entry was: PS 0 (30 patients), PS 1 (12 patients) and PS 2 (2 patients). Stages III/IV were observed in 1/9 patients; the other 34 patients had relapsed after surgery. All 44 patients had been previously treated with a platinum-based regimen. The overall response rate was 25%, 1-year survival rate 52.3%, median survival time 12.6 months and median progression free survival 3.1 months. The major grade 3/4 hematological toxicity was neutropenia (47.7%), and the major grade 3/4 non-hematological toxicity was anorexia (9.1%). All adverse drug reactions seen in the study were manageable. CONCLUSION: Gemcitabine monotherapy is a sufficiently active and well-tolerated therapy for patients who have previously undergone chemotherapy with a platinum-based regimen.     

Gemcitabine in the treatment of advanced head and neck cancer

AimsSeveral new chemotherapy agents show varying degrees of activity in head and neck cancer. One of them is gemcitabine, which is a new nucleoside analogue with an innovative cytostatic mode of action. Gemcitabine has demonstrated a broad spectrum anti-tumoural effect and a favourable toxicity profile. These attributes prompted us to introduce gemcitabine into the treatment of head-and-neck tumours.Materials and methodsTen heavily pre-treated patients with recurrent and incurable squamous-cell carcinoma of the head and neck (SCCHN) were treated with Gem. The initial cycle consisted of six administrations of the drug (1250 mg/m² once weekly intravenously over 30 min) followed by a week without cytotoxic treatment. All following cycles were composed of two infusions once weekly (d1, 8), followed by a week of rest.ResultsToxic effects, length of survival and tumour response was assessable in eight patients owing to one suicide and loss of one patient for follow-up. One complete remission, two partial remissions and three ‘no change’ situations (stable disease) were observed, yielding a response rate of 37.5%. Median survival was 8 months (range 3–12). The incidence of haematological toxicity was low, with grade 3–4 neutropenia in less than 10%. Flu-like symptoms were reported by one-third of patients.ConclusionsIn this small phase-II study, gemcitabine demonstrated a high anti-tumoural activity in SCCHN, with a favourable toxicity profile. Gemcitabine seems to be a promising new drug without severe burden even for patients who are refractory to other cytostatic drugs. Within recent years, the activity and tolerability of gemcitabine was documented in several phase I and phase II trials, especially in combination with cisplatin, and paclitaxel resp, carboplatin/paclitaxel, cisplatin/ifosfamide, and 5-fluorouracil/paclitaxel. The results of these trials will be outlined in the discussion.     

Phase I trial of gemcitabine in patients with advanced pancreatic cancer

BACKGROUND: Gemcitabine is the most promising new agent currently being tested in pancreatic cancer. The present study was conducted to confirm the tolerability of a weekly schedule of gemcitabine at a dose of 1000 mg/m2 in Japanese patients with advanced pancreatic cancer. METHODS: The primary end-point was to evaluate the frequency of dose-limiting toxicity. Gemcitabine 1000 mg/m2 was administered over 30 min weekly in two schedules: gemcitabine x3 every 4 weeks (Schedule 1) and gemcitabine x7 followed by a week of rest and then gemcitabine x3 every 4 weeks thereafter (Schedule 2). At least three patients entered each schedule and three additional patients were treated in the presence of dose-limiting toxicity. RESULTS: Eleven chemo-naive patients with a good Karnofsky performance status of > or =80 points and distant metastasis were entered into this trial. In Schedule 1, no dose-limiting toxicity was observed in the three patients. In Schedule 2, the evaluation of dose-limiting toxicity was complete in six of the eight enrolled patients and two patients showed dose-limiting toxicity in this Schedule; one patient experienced both grade 4 leukocytopenia and grade 4 neutropenia, and both grade 4 neutropenia and grade 3 GOT/GPT increased in another patient. Two patients (18%) showed a partial response and a clinical benefit response was also achieved in two (29%) of the seven evaluable patients. CONCLUSION: Gemcitabine 1000 mg/m2 weekly x7 followed by a week of rest and weekly x3 every 4 weeks thereafter may be tolerated in Japanese patients with advanced pancreatic cancer.     

High efficacy of gemcitabine and cisplatin plus trastuzumab in patients with HER2-overexpressing metastatic breast cancer: a phase II study

AimsEffective and tolerable regimens are sought specifically in women who have been pre-treated with anthracyclines and taxanes. Gemcitabine and cisplatin plus trastuzumab has shown synergistic activity in vitro, and provides a new mechanism of drug interaction. This multicentre phase II study aimed to evaluate the efficacy and tolerability of gemcitabine and cisplatin plus trastuzumab in previously treated patients with metastatic breast cancer (MBC).Materials and methodsPreviously treated patients with human epidermal growth factor receptor 2 (HER2) overexpressing MBC were enrolled in a multicentre phase II study (DAKO Hercep Test 3+). Treatment consisted of gemcitabine (750 mg/m²), cisplatin (30 mg/m²) given on days 1 and 8 every 3 weeks, and trastuzumab (4 mg/kg loading dose, 2 mg/kg weekly).ResultsTwenty patients were recruited, all of whom had previously received chemotherapy (12 pre-treated with taxanes, 18 pre-treated with anthracyclines seven pre-treated with taxanes and trastuzumab). A median of six cycles of the study treatment was delivered. There were eight partial responses, for an overall response rate of 40% (95% confidence interval 16.5–63.5%). The clinical benefit rate (complete response plus partial response plus stable disease) was 80% (95% CI 54.2–95.8%). The response rate in patients who had already received a trastuzumab-based regimen for MBC was 57.1% (95% CI 7.7–100%). Median time to progression was 10.2 months, and median overall survival was 18.8 months. Main toxicities were leukopenia (grade 3 in 55% of patients) and thrombocytopenia (grade 3 in 35% and grade 4 in 5% of patients). Non-haematological toxicity was rarely severe.ConclusionsCombination chemotherapy with gemcitabine and cisplatin plus trastuzumab is well tolerated and active in patients with HER2 overexpressing MBC, even after prior exposure to anthracyclines and taxanes.     

First‐line combination of gemcitabine,oxaliplatin, and L‐asparaginase (GELOX) followed by involved‐field radiation therapy for patients with stage IE/IIE extranodal natural killer/T‐cell lymphoma

BACKGROUND:

Extranodal natural killer/T‐cell lymphoma, nasal type (ENKTL) is a distinct subtype of non‐Hodgkin lymphoma in which the upper aerodigestive tract is the most commonly involved site. To date, optimal treatment strategies and prognosis for patients with ENKTL have not been fully defined.

METHODS:

This prospective study was conducted to evaluate the efficacy and safety profiles of first‐line combined gemcitabine, oxaliplatin, and L‐asparaginase (GELOX) followed by involved‐field radiation therapy for patients with stage IE/IIE ENKTL. The primary endpoints were the complete response rate, the objective response rate, and toxicities. Secondary endpoints were overall survival and progression‐free survival.

RESULTS:

Twenty‐seven patients with newly diagnosed ENKTL were enrolled and completed the entire course of treatment. At the end of treatment, the overall response rate was 96.3%, including 20 patients (74.1%) who attained a complete response and 6 patients (22.2%) who attained a partial response. No patients developed disease progression during therapy. Grade 1 and 2 toxicities were frequent during GELOX, but grade 3 and 4 toxicities were few, and no treatment‐related deaths occurred. At a median follow‐up of 27.37 months, 7 patients (25.9%) experienced disease progression, and 4 of those patients died of disease. The rates of 2‐year overall and progression‐free survival were both 86%, and patients who attained a complete response at the end of treatment had significantly longer progression‐free survival (P = .012) and overall survival (P = .021) than patients who did not attain a complete response.

CONCLUSIONS:

The current results indicated that GELOX followed by involved‐field radiation therapy can be an effective and feasible treatment strategy for patients with stage IE/IIE ENKTL of the upper aerodigestive tract. These results will require further investigation in larger prospective trials. Cancer 2013. © 2012 American Cancer Society.     

Ceravolo

Abstract

Gemcitabine is considered the gold standard treatment for unresectable pancre-atic adenocarcinoma. Intra-arterial drug administration had shown some interesting results in small phase II studies.

In this study, patients were randomly assigned to receive gemcitabine at a dose of 1,000 mg/m² over 30 minutes intravenously weekly for 7 weeks, followed by 1 week of rest, then weekly for 3 weeks every 4 weeks or FLEC: 5-fluoruracil 1,000 mg/m², leucovorin 100 mg/m², epirubicin 60 mg/m², carboplatin 300 mg/m² infused bolus intra-arterially into celiac axis at a 3-week interval 3 times or 5-fluor-ouracil 400 mg/m2 plus folinic acid 20 mg/m2 for 5 days every 4 weeks for 6 cycles. The primary endpoint was overall survival, while time to treatment failure, response rate, clinical benefit response were secondary endpoints. Sixty-seven patients were randomly allocated gemcitabine and 71 were allocated FLEC intra-arterially. Patients treated with FLEC lived for significantly longer than patients on gemcitabine (p=0.036). Survival at 1 year increased from 21% in the gemcitabine group to 35% in the FLEC group. Median survival was 7.9 months in the FLEC group and 5.8 months in the gemcitabine group. Median time to treatment failure was longer with FLEC (5.3 vs 4.2 months for FLEC vs gemcitabine respectively; p=0.013). Clinical benefit was similar in both groups (17.9% for gemcitabine and 26.7% for FLEC; p=NS). CT-scan partial response was similar in both groups (5.9% for gemcitabine and 14% for FLEC; p=NS). Toxicity profiles were different.

Compared with gemcitabine, the FLEC regimen given intra-arterially improved survival in patients with unresectable pancreatic adenocarcinoma.     

Phase II trial of bimonthly leucovorin, 5-fluorouracil and gemcitabine for advanced pancreatic adenocarcinoma (FOLFUGEM)

Background:Gemcitabine alone or 5-fluorouracil (5-FU) according to several schedules are used for palliation of metastatic and locally advanced (LA) pancreatic adenocarcinoma. This study was designed to test the efficacy of the leucovorin–5-FU and gemcitabine combination. Patients and methods:This phase II trial combined a simplified bimonthly LV5FU2 with gemcitabine: leucovorin 400 mg/m² in a two-hour infusion, followed by 5-fluorouracil 400 mg/m² bolus and 2 or 3 g/m² continuous infusion over 46 hours; gemcitabine 1 g/m² was infused over 30 min on day 3 after 5-FU. Treatment was repeated every two weeks. Gemcitabine dose could be increased (250 mg/m² every two cycles up to 1500 mg/m²) in the absence of NCI-CTC toxicity >2. Results:Among the 62 patients included in this study, 22 had LA and 40 had metastatic disease. Objective response rate for the 54 patients with measurable disease was 25.9% (95% confidence interval (CI): 14%–37.8%) and 22.6% (95% CI: 12%–33.2%) in the intent-to-treat population; the clinical benefit rate for the 59 assessable patients was 49.2%. Median progression-free survival and median overall survival were 4.8 and 9 months, respectively, with 32.3% of patients alive at 1 year. The most frequent toxicity (grade 3–4) was neutropenia (56.5%) usually asymptomatic (1.1% febrile neutropenia), but requiring decreases of 5-FU and gemcitabine doses. Unexpected complete alopecia occurred in 97% of patients. Conclusions:Palliative effects, response rate and survival observed in this multicenter study seem to be superior to those obtained with gemcitabine or 5-FU alone, despite a limiting hematological toxicity.     

健择加泰索帝每周给药治疗晚期非小细胞肺癌的临床研究

目的 观察健择联合泰索帝每周给药治疗晚期非小细胞肺癌的疗效，以及两药联合的不良反应。方法 26例经病理学或细胞学确诊的晚期NSCLC患者(初治或复治)接受健择800～1200mg／m^2联合泰索帝35mg／m^2第1、8、15天静脉滴注，每4周重复。2周期以上可评价疗效(包括有效率和中位生存时间)及不良反应。结果 全组CR1例，PR6例，总有效率为27％。其中11例初治患者中5例有效，有效率为45％。中位生存时间9．5个月，1年生存为38％(10／26)。主要不良反应为粒细胞减少及血小板减少。有1例因过敏性休克死己，结论 健择联合泰索帝每周给药治疗晚期非小细胞肺癌疗效与泰索帝三周及四周方案相似，不良反应发乍率明显降低，耐受性较好。     

Single-agent gemcitabine in patients with resistant small-cell lung cancer

Objective:This study was conducted to assess the activity and toxicity of gemcitabine in patients with resistant small-cell lung cancer (SCLC). Patients and methods:Forty-one patients with limited- or extensive-stage SCLC, who were previously treated with at least one chemotherapeutic regimen and progressed during or within three months of finishing the last regimen, were treated with 1000 mg/m² gemcitabine on days 1, 8, and 15 of a four-week cycle. Results:Thirty-eight patients were evaluable for response. Five partial and no complete responses were seen, for an overall response rate of 13% (95% confidence interval (CI): 6%–27%). Time to progression varied from 4 to 20 weeks, with a median of 8 weeks. Median survival was 17 weeks (range 4–84 weeks). Hematological toxicity mainly consisted of NCI–CTC grade 3 thrombocytopenia (29% of patients) and, to a lesser extent, grade 3 leukopenia (18% of patients). Non-hematological toxicity was mild, with nausea being the most commonly reported event. Conclusions:Gemcitabine has modest activity in patients with resistant SCLC. There is some non-cross resistance to most agents against SCLC.     

A phase I clinical trial of low-dose interferon-α-2A, thalidomide plus gemcitabine and capecitabine for patients with progressive metastatic renal cell carcinoma

Background We have conducted a phase I trial to determine the maximum tolerated dose of gemcitabine in combination with interferon, thalidomide and capecitabine. Methods Patients received oral capecitabine 1,000 mg/m² per day, divided in 2 daily doses, 2 weeks on, 1 week off; subcutaneous interferon-α 1 mIU twice a day without an interruption; daily oral thalidomide 200 mg/day for the first 7 days, then escalated to 400 mg/day without an interruption. Gemcitabine was given by intravenous administration over 30 min on day 1, week 1 and day 8, week 2. Initial dose level of gemcitabine was 400 mg/m². The dose of gemcitabine was the phase I variable. One cycle was 3 weeks. Results and discussion We treated 12 patients, 6 patients were entered at a dose level of 0 (gemcitabine 400 mg/m²) and 6 patients entered at a dose level-1 (gemcitabine 200 mg/m²). Eight of 12 patients completed at least 12 weeks of therapy. Three partial responses and two stable disease were observed. The remaining patients had progressive disease. Non-hematologic toxicity was either grade 1 or 2. Hematologic toxicity at dose level 0 consisted of 3 patients with grade 3/4 neutropenia, and 1 patient with grade 3 thrombocytopenia. At dose level-1 grade 1/2 neutropenia was observed. Conclusions The completion of our phase I experience determined our maximum tolerated dose to be dose level-1. The phase II trial is currently being proposed for patients with rapidly growing clear cell, other histologies that may contain sarcomatoid elements or collecting duct tumor.     

Phase II study of gemcitabine in ovarian cancer

This phase II study evaluated the response rate and toxicity of single-agent gemcitabine in 40 women with epithelial ovarian cancer, previously treated with platinum-based chemotherapy. Patients had stage III or IV disease and progressive disease 1–12 months after the last treatment. Gemcitabine 1250 mg/m² was administered on days 1, 8 and 15 of each 28-day cycle as a 30-minute infusion.The overall response rate to gemcitabine was 22% (95% confidence intervals: 10–39%). Responses to gemcitabine were observed in patients with platinum-refractory disease, which suggests no cross resistance to platinum. Gemcitabine was well tolerated and no grade 4 toxicity was seen.This study confirms that gemcitabine is active and well tolerated in pre-treated women with ovarian cancer.     

Gemcitabine and vinorelbine in recurrent advanced non-small cell lung cancer: sequence does matter

Summary Purpose Gemcitabine and vinorelbine have demonstrated clinical efficacy both as single agents and in combination in patients with metastatic non-small cell lung cancer (NSCLC). This phase II trial evaluated biweekly gemcitabine and vinorelbine in NSCLC patients who have had one prior chemotherapeutic regimen and have had disease progression. Methods Gemcitabine (1,200 mg/m² IV over 30 min) was followed by vinorelbine (30 mg/m² IV over 6–10 min) on days 1 and 15 of each 28 day cycle. Chemotherapy was given for six cycles unless disease progression or unacceptable toxicity was seen. Results From 11/1998 to 10/2000, 15 of 20 patients enrolled (6 males, 9 females) were evaluable for response and survival. Two patients had grade 4 neutropenia, and one patient had grade 4 thrombocytopenia. The only non-hematologic grade 3 toxicities were fatigue, phlebitis, and arthralgias. No objective responses were observed, but 11 patients had stable disease for a mean of 6 months. The median survival time was 9.4 months (95% CI = 4.2, 14.8), with a median time to progression of 4.2 months (95% CI = 1.9, 5.6). The 1 year survival was 47%. Conclusions While this schedule of gemcitabine and vinorelbine was well tolerated, it was felt to be inactive. In vitro and pharmacokinetic studies published after the completion of our trial, suggest gemcitabine followed by vinorelbine may have antagonistic effects leading to lower dose delivery of both drugs. Our study was the only study of gemcitabine and vinorelbine in second-line NSCLC in the literature without an objective response. Our study was the only second-line study that administered gemcitabine prior to vinorelbine. First-line studies in the literature that administered vinorelbine prior to gemcitabine had, on average, a 1.7 month higher median survival (10.0 vs. 8.3 mos; P value <0.001). Because of the lack of response, further studies using this drug sequence, dose, and schedule for gemcitabine and vinorelbine are not recommended.     

Gemcitabine in bone sarcoma resistant to Doxorubicin-based chemotherapy

Subjects and Methods: Seven patients with progressive localized or metastatic chemo-resistant osteosarcoma were treated by gemcitabine.The protocol included gemcitabine 1000 mg/m2/w for 7 consecutive weeks, followed by 1 week rest. If no progression was observed,maintenance by gemcitabine 1000 mg/m2/w for 3 weeks every 28 days was given until failure was clinically or radiologically evident.Results. The true objective response rate was 0%. However, disease stabilization and clinical benefit response were observed in five patients (70%) for 13-96 weeks.Discussion. Postponing the inevitable death with a relatively non-toxic treatment, is, in our opinion, an important issue especially in young patients.Thus it may be justified and warranted to investigate the activity of gemcitabine in a larger group of patients with bone sarcomas.     

Phase II study on gemcitabine in recurrent and/or metastatic adenoid cystic carcinoma of the head and neck (EORTC 24982)

BackgroundThis phase II study was conducted to determine the antitumour activity of gemcitabine in adenoid cystic carcinoma (ACC).Patients and methodsPatients with progressive and/or symptomatic, recurrent and/or metastatic ACC were treated with gemcitabine 1250 mg/m² intravenous (i.v.) on days 1 and 8 of each 21-day cycle. Each cycle was repeated every 3 weeks in the absence of disease progression for a minimum of four cycles and a maximum of 12 cycles.ResultsAmong 21 ACC patients, there were no objective responses. Eleven patients had a stable disease, of which ten patients for more than 6 months, and eight had a progressive disease after 4 cycles. Gemcitabine was well tolerated by most patients.ConclusionWe conclude that gemcitabine is not an active drug in ACC.     

Gemcitabine in advanced pancreatic cancer: a phase II trial

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

High efficacy of gemcitabine and cisplatin in patients with predominantly anthracycline- and taxane-pretreated metastatic breast cancer

Background: Effective and tolerable regimens are sought specifically in patients who have been pretreated with anthracyclines and taxanes. Gemcitabine and cisplatin demonstrated synergistic activity in vitro and provides a new mechanism of drug interaction. Patients and methods: Previously treated patients with metastatic breast cancer (MBC) were enrolled in a multicentre phase II study. Treatment consisted of gemcitabine (750 mg/m²) and cisplatin (30 mg/m²) given on day 1 and 8 every 3 weeks. Results: Thirty-eight patients were recruited, all of whom had previously received chemotherapy (35 pretreated with taxanes, 33 pretreated with anthracyclines). A median of 5 cycles of the study treatment was delivered. There were 2 complete and 13 partial responses, for an overall response rate of 40% (95% confidence interval: 23–56%). Thirteen patients (35%) had stable disease. Tumour response appeared independent of previously applied chemotherapy. Median time-to-progression was 6 months and median overall survival was 13.5 months. Main toxicities were leucopenia and thrombocytopenia (grade 3/4 in 26 and 16% of cycles, respectively). Non-haematological toxicity was rarely severe. Conclusions: Combination chemotherapy with gemcitabine and cisplatin given on 2 out of 3 weeks is well tolerated and active in heavily pretreated patients with MBC, even after prior exposure to anthracyclines and taxanes. V. Heinemann, H.J. Stemmler contributed equally     

Gemcitabine in advanced angiosarcoma: a retrospective case series analysis from the Italian Rare Cancer Network

BackgroundAngiosarcoma is a highly aggressive soft tissue sarcoma. Responses to anthracyclines plus/minus ifosfamide, and taxanes alone or in combination with gemcitabine are well documented. Very few data are available on gemcitabine as a single agent.Patients and methodsWe retrospectively reviewed all cases of advanced progressive angiosarcoma treated with gemcitabine as a single agent (1000 mg/m² i.v. every week for 3 weeks every 4 weeks), at Istituto Nazionale Tumori and within the Italian Rare Cancers Network from January 2008 to November 2010.ResultsTwenty-five patients [mean age: 52 years; radiation therapy (RT)-related: 8] received gemcitabine. Best tumor response by RECIST was as follows: complete response = 2, partial response = 14, stable disease = 2, progressive disease = 7 cases, for an overall response rate (PR + CR) of 68%. Six of eight post-RT angiosarcomas responded to treatment. Median overall survival (OS) was 17 months. Median progression-free survival (PFS) was 7 months (range 1–40 months). One patient with a locally advanced thyroid angiosarcoma became resectable after 5 months of gemcitabine, with <10% residual viable tumor cells seen on surgical specimen. Overall, gemcitabine was well tolerated.ConclusionsGemcitabine is active in both RT- and non-RT-related angiosarcoma, with dimensional and possibly long-lasting responses. A formal phase II study on gemcitabine as a single agent is warranted.     

A Phase II trial of fixed dose rate gemcitabine in patients with advanced biliary tree carcinoma

Gemcitabine is a commonly used chemotherapy for biliary tree carcinomas, achieving response rates of 10% to 60%. Preclinical studies indicate that fixed dose rate infusion optimizes accumulation of gemcitabine triphosphate and may enhance the clinical activity of gemcitabine. We conducted a phase II study of fixed dose rate gemcitabine in 15 chemotherapy-naive patients with advanced cholangiocarcinoma and gallbladder carcinoma. Gemcitabine was administered at a dose of 1500 mg/m2 over 150 minutes weekly for 3 weeks every 28 days. Fourteen patients were evaluable for response. No complete or partial responses were observed. Two patients (13%) had stable disease lasting a median of 9 weeks. The median time to progression was 9 weeks; median survival was 20 weeks. There was considerable grade 3/4 hematologic toxicity, including neutropenia in 49% of patients, leukopenia in 40%, anemia in 27%, and thrombocytopenia in 27%. Grade 3/4 nonhematologic toxicities were minimal. We conclude that fixed dose rate gemcitabine results in significant myelosuppression and has minimal activity in patients with biliary tree carcinoma.     

Gemcitabine and oxaliplatin combination chemotherapy for metastatic well‐differentiated neuroendocrine carcinomas

BACKGROUND:

Beyond the usual regimens based on streptozocin and doxorubicin or 5‐fluorouracil, no second‐line therapy of metastatic neuroendocrine tumor has gained wide acceptance. Gemcitabine and oxaliplatin are generally well tolerated and have shown activity against a wide range of malignancies. The authors assessed the efficacy of gemcitabine‐oxaliplatin combination (GEMOX) in the treatment of patients with metastatic neuroendocrine tumors.

METHODS:

Twenty consecutive patients with progressive disease were treated with GEMOX, in most cases after failure of other chemotherapy regimens (median = 2). Patients were followed for evidence of toxicity, response, and survival. Two patients were chemotherapy‐naive at treatment initiation and were excluded from the efficacy analysis.

RESULTS:

Toxicity was manageable overall; however, 6 (30%) patients had to discontinue treatment because of oxaliplatin‐induced neurotoxicity (grade 2). Three (17%) of 18 patients had a partial response, median progression‐free survival was 7.0 months, and median overall survival was 23.4 months.

CONCLUSIONS:

Gemcitabine‐oxaliplatin combination shows interesting activity and is well tolerated in pretreated patients with neuroendocrine tumors. Cancer 2009. © 2009 American Cancer Society.