Gemcitabine and cisplatin in the treatment of advanced or metastatic pancreatic cancer

Background:This phase II study was initiated to determine theefficacy and safety of gemcitabine plus cisplatin in patients with pancreaticcancer. Patients and methods:Gemcitabine 1000 mg/m² was givenon days 1, 8, and 15 of a 28-day schedule, and cisplatin 50 mg/m²on days 1 and 15 to chemonaive patients with locally advanced or metastaticpancreatic cancer. Results:Of the 41 patients enrolled (median age 57, and61% male), median Karnofsky performance status was 80%. Patientsreceived a median of 4.2 cycles (range 1–11). In 35 evaluable patients,one complete response (CR) and three partial responses (PR) were observed, foran overall response rate of 11% (95% confidence interval(95% CI): 3.2%–26.7%). Stable disease (SD) >3months occurred in 20 (57%) patients; 6 survived 1 year. Mediantime to progressive disease was 4.3 months (95% CI: 3.0–5.7months). For all patients, median survival was 8.2 months (95% CI:6.1–10.6 months) with a one-year survival rate of 27%. Therapywas well tolerated. Grade 3–4 neutropenia (no grade 3–4infection), thrombocytopenia (no bleeding), nausea/vomiting, and alopecia werereported in 29%, 13%, and 2.6% of patients, respectively. Conclusions:The combination of gemcitabine and cisplatin is amoderately active treatment for patients with locally advanced and metastaticpancreatic cancer without compromising tolerability.     

晚期胰腺癌姑息性化疗进展

胰腺癌的恶性程度极高且预后极差,其病死率约占年发病人数的98％。以联合放化疗为主的综合治疗是局部晚期及转移性胰腺癌主要的治疗手段,但疗效有限。多项研究结果以及荟萃分析证实了吉西他滨在晚期胰腺癌中应用的优势,目前吉西他滨已成为晚期胰腺癌一线化疗的首选药物。虽然以吉西他滨为基础的联合方案被广泛应用于晚期胰腺癌的治疗,但仍缺乏足够的循证医学证据支持联合方案优于单药,所以最佳化疗的手段及方案仍需进一步研究证实。随着新的化疗药物以及靶向药物的出现,给晚期胰腺癌患者带来了新的希望。     

Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer: results of secondary end points analyses

In advanced pancreatic cancer, level one evidence has established a significant survival advantage with chemotherapy, compared to best supportive care. The treatment-associated toxicity needs to be evaluated. This study examines the secondary outcome measures for chemotherapy in advanced pancreatic cancer using meta-analyses. A systematic review was undertaken employing Cochrane methodology, with search of databases, conference proceedings and trial registers. The secondary end points were progression-free survival (PFS)/time to progression (TTP) (summarised using the hazard ratio (HR)), response rate and toxicity (summarised using relative risk). There was no significant advantage of 5FU combinations vs 5FU alone for TTP (HR=1.02; 95% CI=0.85-1.23) and toxicity. Progression-free survival (HR 0.78; CI 0.70-0.88), TTP (HR=0.85; 95% CI=0.72-0.99) and overall response rate (RR=0.56; 95% CI=0.46-0.68) were significantly better for gemcitabine combination chemotherapy, but offset by the greater grade 3/4 toxicity thrombocytopenia (RR=1.94; 95% CI=1.32-2.84), leucopenia (RR=1.46; 95% CI=1.15-1.86), neutropenia (RR=1.48; 95% CI=1.07-2.05), nausea (RR=1.77; 95% CI=1.37-2.29), vomiting (RR=1.64; 95% CI=1.24-2.16) and diarrhoea (RR=2.73; 95% CI=1.87-3.98). There is no significant advantage on secondary end point analyses for administering 5FU in combination over 5FU alone. There is improved PFS/TTP and response rate, with gemcitabine-based combinations, although this comes with greater toxicity.     

Improved survival with induction chemotherapy and conversion surgery in locally advanced unresectable pancreatic cancer: a single institution experience

Both efficacy and tolerability are critical issues in choosing neoadjuvant chemotherapy in patients with unresectable locally advanced pancreatic cancer (LAPC). The optimal regimen and the impact of conversion surgery on patient survival remains insufficiently reported in Asain population. Therefore, we conducted a retrospective study aiming to evaluate the resection rate after different induction chemotherapy regimen and its impact toward survival. All patients with pancreatic cancer treated in our institute from 2013 to 2020, a total of 730 patients, were reviewed and 131 patients with LAPC were identified. For cohort homogeneity, 14 patients receiving induction concurrent chemoradiotherapy initially were excluded and 117 patients receiving induction chemotherapy were included in the study. Most patients (90 of 117, 77%) received triplet induction chemotherapy, including the combination of S1, leucovorin, oxaliplatin and gemcitabine (SLOG) in 48, modified FOLFIRINOX in 21 and the combination of gemcitabine, oxaliplatin, fluorouracil and leucovorin (GOFL) in 21. The tumor response rate (19%-33%), the surgical exploration rate (38%-52%) and the mOS (15.4-23.0 months) were not significantly different among the three triplets. Both GOFL and SLOG regimen had comparable efficacy and less neutropenia as compared to mFOLFIRINOX. Conversion surgery was performed in 34 of 117 (29%) patients after induction chemotherapy. The median overall survival (mOS) in patients with and without conversion surgery were 29.1 and 14.1 months, respectively (P<0.0001). Radiological response alone was not a reliable indicator of successful conversion surgery. Patients who underwent conversion surgery had significantly better survival and thus highlighted the importance of surgical exploration in all patients who did not have progressive disease after induction chemotherapy.     

Raltitrexed-eloxatin salvage chemotherapy in gemcitabine-resistant metastatic pancreatic cancer

Limited information on salvage treatment in patients affected by pancreatic cancer is available. At failure, about half of the patients present good performance status (PS) and are candidate for further treatment. Patients >18 years, PS >or=50, with metastatic pancreatic adenocarcinoma previously treated with gemcitabine-containing chemotherapy, and progression-free survival (PFS) <12 months received a combination of raltitrexed (3 mg m(-2)) and oxaliplatin (130 mg m(-2)) every 3 weeks until progression, toxicity, or a maximum of six cycles. A total of 41 patients received 137 cycles of chemotherapy. Dose intensity for both drugs was 92% of the intended dose. Main grade >2 toxicity was: neutropenia in five patients (12%), thrombocytopenia, liver and vomiting in three (7%), fatigue in two (5%). In total, 10 patients (24%) yielded a partial response, 11 a stable disease. Progression-free survival at 6 months was 14.6%. Median survival was 5.2 months. Survival was significantly longer in patients with previous PFS >6 months and in patients without pancreatic localisation. A clinically relevant improvement of quality of life was observed in numerous domains. Raltitrexed-oxaliplatin regimen may constitute a treatment opportunity in gemcitabine-resistant metastatic pancreatic cancer. Previous PFS interval may allow the identification of patients who are more likely to benefit from salvage treatment.     

动脉灌注化疗并同期放疗的综合治疗中晚期胰腺癌

目的观察动脉灌注化疗并同期放疗的综合治疗中晚期胰腺癌的作用。方法９２年１月至９６年１月收治５２例中晚期胰腺癌,２３例行动脉灌注化疗并同期放疗（综合组）,２９例行单纯放疗（单放组）。单放组每周照５次,每次１８０－２００ｃＧＹ,总量５０００－６０００ｃＧＹ／５－６．７周,综合组动脉灌注化疗,每次５－Ｆｕ１．０、ＭＭＣ１０ｍｇ、ＤＤＰ６０ｍｇ,每４周一次,平均２．３次／人,同期放疗方案同单放组。结果腹痛、黄疸的症状缓解率两组之间无明显差异,但综合组黄疸改善时间较长（１３个月对５个月Ｐ＜０．０５）;肿瘤缩小率达５０％以上综合组６９．６％（１６／２３）,单放组３７．９％（１１／２９）;两组１、２、３年生存率分别为７８．５％、３７．１％、２６．７％和５２．３％、２２．９％、１０．５％,综合组明显好于单放组。结论不能手术切除的中晚期胰腺癌通过动脉灌注化疗并同期放射治疗的综合治疗较单放组能获得较高的生存率。     

Treatment options for advanced pancreatic cancer: a review

Advanced pancreatic adenocarcinoma historically has a poor prognosis and the mortality rate has remained unchanged for over a decade. Common treatment options for patients with advanced pancreatic cancer include chemoradiation and/or chemotherapy. Single-agent gemcitabine has been considered the standard of care since 1997. Recently published findings indicate that the oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX) treatment regimen significantly improves overall survival compared with gemcitabine. Research has shifted to focus on understanding the causes the resistance of pancreatic cancer to chemotherapy and potential methods to overcome it. This review will focus on the current treatment options, the evolution of targeted therapy, novel agents on the horizon and potential options to ameliorate chemoresistance.     

吉西他滨单药化疗与联合化疗治疗进展期胰腺癌的疗效观察

目的观察比较吉西他滨单药与联合化疗治疗进展期胰腺癌的疗效。方法回顾性分析了大连医科大学附属一院2002年至2009年收治的45例进展期胰腺癌患者的临床资料,吉西他滨单药组17例,剂量为1000mg/m2,d1、8,三周为一周期;吉西他滨联合治疗组28例,联合化疗方案包括吉西他滨1000mg/m2,d1、8,分别联合：（1）氟尿嘧啶425～600mg/m2,静滴或持续静脉泵入,d1～5;（2）顺铂60～75mg/m2,分3～4d静脉滴入;（3）奥沙利铂85～130mg/m2,d1,静脉滴入;（4）卡培他滨1000mg/m2,每天两次口服,d1～14。21d为一周期。采用Kaplan-Meier生存曲线分析患者的生存期,并比较两组间的临床受益率、中位疾病进展时间、中位生存时间及不良反应。结果吉西他滨联合组及单药组的临床收益率均得到提高,但两组间比较临床受益率、疾病控制率、中位生存时间均无统计学意义。结论吉西他滨联合化疗方案与吉西他滨单药治疗进展期胰腺癌相比,疗效、临床受益率、中位生存期均相似。     

以健择为主介入治疗联合化疗治疗晚期胰腺癌20例

目的探讨以健择为主介入治疗联合全身化疗治疗晚期胰腺癌的疗效。方法在X光监视下将导管插入十二指肠上下动脉,将健择1000mg／m^2以0．9％氯化钠溶液（NS）溶解后每次注入1/2量,氟脲苷（FUDR）0．5g、顺铂（DDP）60mg同样以0．9％氯化钠溶液（NS）溶解后每次靶动脉注入1／2量,d2～d5予全身联合化疗,28d为1周期,完成3个周期评价疗效。结果全组无CR病例,PR11例（55％）,NC6例（30％）,总有效率为55％。结论健择为主介入治疗联合全身化疗治疗晚期胰腺癌有较好的疗效,同时能减轻症状,提高病人的生存质量,但确切疗效有待扩大样本进一步探讨。     

替吉奥联合吉西他滨治疗晚期胰腺癌的疗效观察

目的:探讨替吉奥(S-1)胶囊联合吉西他滨(GEM)化疗与吉西他滨单药治疗进展期胰腺癌的疗效.方法:对2011年5月至2013年5月收治的37例晚期胰腺癌患者的临床资料进行回顾性分析,其中18例采用替吉奥胶囊联合吉西他滨方案治疗(治疗组);19例采用吉西他滨单药治疗(对照组).采用Kaplan-Meier法分析患者的生存时间,并比较两组患者的客观缓解率、临床受益反应(CBR)、中位疾病进展时间、中位生存时间和不良反应.结果:治疗组有效率明显高于对照组(33.3％vs 21.1％),差异有统计学意义(P =0.032).治疗组疾病控制率(DCR)高于对照组(72.2％vs 63.2％),但差异无统计学意义(P =0.450).治疗组患者CBR缓解率高于对照组(71.8％ vs 45.7％),差异无统计学意义(P=0.421).治疗组的中位生存时间为10.1个月(95％CI:8.0-11.5个月),高于对照组的8.02个月(95％ CI:3.7-10.8个月),差异有统计学意义(P=0.043);两组的中位疾病进展时间分别为3.5个月和3.0个月(P=0.720).治疗组的6个月生存率(72.5％)略高于对照组(66.5％),但差异无统计学意义(P＞0.05).两组不良反应的发生率也相似(P＞0.05).结论:替吉奥胶囊联合吉西他滨治疗方案与单药治疗晚期胰腺癌相比,在客观疗效、中位生存时间方面表现出一定优势,疾病控制率及临床受益反应也有所提高,且不良反应可耐受,是晚期胰腺癌的有效治疗方案.     

中药加化疗治疗局部晚期胰腺癌的疗效分析

观察中医药加由健择和顺铂组成的化疗方案时局部晚期胰腺癌的疗效。遵照患者意愿,有选择地将37例局部晚期胰腺癌患者分为治疗组(中西医结合组)和对照组(单纯化疗组)。治疗组化疗期间和化疗后继续服中药巩固疗效。结果两组近期疗效差异无统计学意义,临床获益率和远期疗效治疗组明显优于对照组,P<0．01。初步研究结果提示,中医药配合化疗可提高局部晚期胰腺癌的临床获益率,延长生存期。     

吉西他滨联合奥沙利铂治疗晚期胰腺癌的临床观察

为观察吉西他滨（GEM）联合奥沙利铂（OXA）治疗晚期胰腺癌的有效性和安全性。对30例晚期胰腺癌患者,应用GEM1000mg/m2,静脉滴入30min,d1、d8;OXA100mg/m2,静脉滴入2h,d1,21d重复。至少接受2个周期的化疗。结果30例均可评价疗效,客观有效率20.00%,临床受益疗效分别为疼痛缓解率53.33%（16/30）,行为状态改善率45.33%（13/30）,体质量状态改善率36.33%（10/30）。主要不良反应为骨髓抑制、外周神经毒性及胃肠道反应,无治疗相关性死亡。初步研究结果显示,GEM联合OXA组成的GEMOX方案治疗晚期胰腺癌近期有效率较高,毒性较低,值得临床推广应用。     

Systemic therapy for advanced pancreatic cancer

Death from pancreatic cancer remains high with few long-term survivors. Systemic chemotherapy with 5-fluorouracil-based combinations had minimal impact on natural history of this disease. Several new agents with activity against pancreatic cancer have been identified over the past decade. Gemcitabine has modest activity in this disease. Combination chemotherapy trials incorporating gemcitabine, cisplatin, 5-fluorouracil, oxaliplatin, docetaxel or irinotecan show improved outcomes in objective response rates and survival that need to be confirmed in prospectively randomized studies. Advancement in the understanding of the biology of pancreatic cancer has helped identify several molecular targets for the development of novel therapies. Ongoing and future treatment regimens for pancreatic cancer will incorporate traditional cytotoxic drugs and novel targeted therapies.     

Maintenance treatment in metastatic breast cancer

Metastatic breast cancer (MBC) occurs in 20–30% of women with breast cancer and is an incurable disease. Treatment is palliative and directed to prolong survival, decrease symptoms and improve patients’ quality of life. For patients with hormone receptor-negative disease or for hormone receptor-positive disease that has become resistant to endocrine therapy, or is progessing rapidly and life threatening, cytotoxic chemotherapy is indicated. However, the optimal duration of chemotherapy treatment for MBC is still a matter of debate. Studies using maintenance chemotherapy regimens standard in the 1990s showed a consistent benefit with a more prolonged time to progression, although an improvement in survival was only demonstrated in one study. Two recent trials with newer cytotoxic agents showed controversial results; whereas one study concluded that the policy of prolonging treatment in chemotherapy-sensitive patients, after aggressive, modern combination chemotherapy, cannot be recommended for women with MBC, the other study showed that maintenance therapy with pegylated liposomal doxorubicin significantly prolonged time to progression in MBC patients after first-line chemotherapy without significant clinical toxicity. Initial data regarding metronomic chemotherapy indicate that continuously low-dose cyclophosphamide and methotrexate is minimally toxic and effective in heavily pretreated breast cancer patients. In daily practice, maintenance chemotherapy is a reasonable strategy that prolongs time to progression in patients with MBC who did not show progression after first-line chemotherapy. However, this benefit should be considered together with toxicities of treatment and the patient’s preference.     

中晚期胰腺癌动脉灌注化疗并同期放疗的疗效观察

目的 分析中晚期胰腺动脉灌注化疗并同期放疗与单纯放疗的疗效。方法 对１９９２年１月至１９９５年１０月行动脉灌注化疗并同期放疗（综合组）的２２例和单纯放疗（单放组）的２８例中晚期胰腺癌的疗效进行比较分析,两组临床资料具可比性,单放组每周照５次,每次ＤＴ１．８～２．０Ｇｙ,总量５０～６０Ｇｙ／５～６．７周,综合组动脉灌注化疗,每次５－Ｆｕ,１．０ｇ,ＭＭＣ１０ｍｇ,ＤＤＰ６０ｍｇ,每４周一次,平均２．     

间质化疗在胰腺癌治疗中的应用

胰腺癌早期诊断困难,手术切除率低。放化疗是进展期胰腺癌的主要治疗手段,但是疗效不能令人满意。间质化疗是一种局部治疗手段,目前主要应用于头颈部肿瘤、肝癌等的治疗。针对胰腺癌间质化疗的一系列动物实验都取得了很好的结果,提示间质化疗的合理应用,会成为进展期胰腺癌的有效治疗手段。     

Induction chemotherapy selects patients with locally advanced, unresectable pancreatic cancer for optimal benefit from consolidative chemoradiation therapy

BACKGROUND: The current study was conducted to determine whether there were differences in outcome for patients with unresectable locally advanced pancreatic cancer (LAPC) who received treatment with chemoradiation therapy (CR) versus induction chemotherapy followed by CR (CCR). METHODS: Between December 1993 and July 2005, 323 consecutive patients with LAPC were treated at the authors' institution with radiotherapy and concurrent gemcitabine or fluoropyrimidine chemotherapy. Two hundred forty-seven patients received CR as initial treatment, and 76 patients received a median of 2.5 months of gemcitabine-based induction chemotherapy prior to CR. Most patients received a radiation dose of 30 grays in 10 fractions (85%) concurrently with infusional 5-fluorouracil (41%), gemcitabine (39%), or capecitabine (20%). RESULTS: The median follow-up was 5.5 months (range, 1-63 months). For all patients, the median overall survival (OS) and progression-free survival (PFS) were 9 months and 5 months, respectively, and the 2-year estimated OS and PFS rates were 9% and 5%, respectively. The median OS and PFS were 8.5 months and 4.2 months, respectively, in the CR group and 11.9 months and 6.4 months, respectively, in the CCR group (both P < .001). The median times to local and distant progression were 6.0 months and 5.6 months, respectively, in the CR group and 8.9 and 9.5 months, respectively, in the CCR group (P = .003 and P = .007, respectively). There was no significant difference in the patterns of failure with the use of induction chemotherapy. CONCLUSIONS: The results from this analysis indicated that, by excluding patients with rapid distant progression, induction chemotherapy may select patients with LAPC for optimal benefit from consolidative CR. The authors believe that this strategy of enriching the population of patients who receive a locoregional treatment modality merits prospective randomized evaluation.     

Adjuvant chemotherapy in elderly patients with pancreatic cancer

Background:

Adjuvant chemotherapy improves survival for patients with resected pancreatic cancer. Elderly patients are under-represented in Phase III clinical trials, and as a consequence the efficacy of adjuvant therapy in older patients with pancreatic cancer is not clear. We aimed to assess the use and efficacy of adjuvant chemotherapy in older patients with pancreatic cancer.

Methods:

We assessed a community cohort of 439 patients with a diagnosis of pancreatic ductal adenocarcinoma who underwent operative resection in centres associated with the Australian Pancreatic Cancer Genome Initiative.

Results:

The median age of the cohort was 67 years. Overall only 47% of all patients received adjuvant therapy. Patients who received adjuvant chemotherapy were predominantly younger, had later stage disease, more lymph node involvement and more evidence of perineural invasion than the group that did not receive adjuvant treatment. Overall, adjuvant chemotherapy was associated with prolonged survival (median 22.1 vs 15.8 months; P<0.0001). Older patients (aged ⩾70) were less likely to receive adjuvant chemotherapy (51.5% vs 29.8% P<0.0001). Older patients had a particularly poor outcome when adjuvant therapy was not delivered (median survival=13.1 months; HR 1.89, 95% CI: 1.27–2.78, P=0.002).

Conclusion:

Patients aged ⩾70 are less likely to receive adjuvant therapy although it is associated with improved outcome. Increased use of adjuvant therapy in older individuals is encouraged as they constitute a large proportion of patients with pancreatic cancer.     

Role of systemic chemotherapy in metastatic cervical cancer

Cervical cancer is a chemoresponsive tumor. Concurrent chemotherapy with cisplatin and radiotherapy has resulted in improved survival in patients with locally advanced cervical cancer and is now standard of care. There are many active drugs in metastatic cervical cancer with cisplatin being the most active single agent. Although response rates are significantly higher with cisplatin combinations, to date, there is no evidence to suggest this is associated with an improved survival. However, this is still an area that is attracting much research interest. The role of chemotherapy in metastatic cervical cancer will be reviewed together with some of the new areas of research.     

晚期非小细胞肺癌的维持化疗

维持化疗对晚期非小细胞肺癌(NSCLC)可延长生存期.诱导化疗方案中证实有效的药物可用于维持化疗,二线、三线化疗药物及分子靶向药物似乎更适合用于晚期NSCLC维持化疗.