Neoadjuvant chemotherapy with a combination of irinotecan and cisplatin in advanced gastric cancer--a case report

We report a case of advanced gastric carcinoma successfully treated with a combination of irinotecan and cisplatin as neoadjuvant chemotherapy. The patient, a 78-year-old man, had type 2 gastric cancer, which had metastasized to the paraaortic lymph nodes. He was treated with irinotecan, 70 mg on day 1 and day 15, and cisplatin, 80 mg on day 1. The course was repeated every 4 weeks. Two courses of treatment resulted in a marked reduction of both the primary tumor and lymph nodes. Subsequently, the patient underwent curative surgery consisting of total gastrectomy, splenectomy, and D3 lymph node dissection. No surgical complications were observed. On microscopic examination, only a few tumor cells were detected in the granulation tissues of the resected stomach and in the lymph nodes. This would be the first case to demonstrate the effectiveness and the safety of irinotecan and cisplatin used in the neoadjuvant setting for treatment of advanced gastric carcinoma.     

Phase I study of paclitaxel and cisplatin for patients with advanced or recurrent gastric cancer

BACKGROUND/AIMS: The present phase I study was planned to define the toxicities, maximum tolerated dose (MTD), and pharmacokinetics of the combination of paclitaxel and cisplatin in patients with advanced or recurrent gastric cancer, and to recommend a dose for the phase II study. METHODOLOGY: Patients were required to have performance status of 0 to 1, to be between 15 and 74 years of age, and to have adequate organ function. The cisplatin was administered at a fixed dose of 25mg/m2 and paclitaxel was administered at four dose levels (60, 70, 80, and 90mg/m2). Plasma sampling was performed to characterize the pharmacokinetics and pharacodynamics of paclitaxel. RESULTS: All of the 15 patients entered were assessable for toxicity and response and were subject to analysis of dose-limiting toxicity (DLT) and MTD. Neutropenia (grade 4, for 3 days or more; n=2) indicated DLT at dose level 4 (90mg/m2). The MTD for this regimen was 90mg/m2/week of paclitaxel for 3 weeks. Tumor response occurred in 7 of the 15 patients and the overall response rate was 57.1%. The pharmacokinetic profiles of paclitaxel were similar to those observed after the administration of each dose as a single agent. CONCLUSIONS: Our study demonstrated that the level 3 dosage (80mg/m2 of paclitaxel and 25mg/m2 of cisplatin) is recommended for this combination chemotherapy. This phase I study showed favorable antitumor activity and fewer adverse reactions relative to other types of chemotherapy.     

Combination chemotherapy using TS-1, Paclitaxel and cisplatin for multiple lung metastases from AFP-producing gastric cancer: a case report

A 61-year-old male had undergone distal gastrectomy followed by right hepatectomy for alpha-fetoprotein-producing gastric cancer and liver metastasis. Subsequently, multiple lung metastases were detected by follow-up chest examinations. Despite treatment with TS-1/Irinotecan (CPT-11)/Cisplatin (CDDP) combination therapy, the metastases increased gradually in size and number. Combination therapy with TS-1/Paclitaxel (TXL)/CDDP was effective, as confirmed by marked reduction in tumor size on chest computed tomography. TS-1/TXL/CDDP chemotherapy was administered repeatedly for relapse of lung metastases. The relapse was controlled twice with this chemotherapy regimen, and the patient remains alive at 52 months after gastrectomy without pulmonary symptoms such as hemosputum. Although patients with postoperative lung metastases from AFP-producing gastric cancer have a dismal prognosis, our clinical experience suggests that TS-1/TXL/CDDP combination therapy may be a useful regimen for such conditions.     

Advanced gastric cancer with peritoneal dissemination successfully treated with paclitaxel and doxifluridine: a case report

A 50-year-old female presenting with severe ascites and anemia and diagnosed with advanced gastric cancer was admitted to our hospital. Endoscopic examination revealed an edematous lesion with redness and a giant fold in the stomach with poor expansion. The histological examination of biopsy specimens from the edematous lesion revealed signet-ring-cell carcinoma. Computed tomography demonstrated a thickening of the gastric wall, severe ascites, and peritoneal dissemination in the Douglas pouch. Paclitaxel (70mg/m2) was administered to the patient on days 1, 8, and 15, with doxifluridine (533mg/m2) for five days per week, on a 28-day cycle. By completion of the first course of treatment, the ascites had disappeared, the tumor in the Douglas pouch had shrunk, and the thickening of the gastric wall had lessened. In addition, the fold in the stomach appeared by endoscopic examination to have resumed its normal thickness, no malignant cells were detected in a biopsy, and the thymidine phosphorylase activity in the tumor tissue was two-fold greater than that before chemotherapy. After three treatment courses, the number of apoptotic cells had apparently increased compared with the prechemotherapy number. The only adverse drug reactions that were observed were grade 2 alopecia and grade 1 myalgia. After thirteen courses of chemotherapy over the past one year, both primary and metastatic lesions seem to be regressing. This case study suggests that paclitaxel plus doxifluridine therapy is effective and well-tolerated in non-resectable gastric cancer patients.     

Pharmacokinetics of paclitaxel in a hemodialysis patient with advanced gastric cancer： A case report

We report for the first time the possibility of weekly paclitaxel chemotherapy for a patient with advanced, nonresectable gastric cancer undergoing hemodialysis. A 50-year-old man with chronic renal failure due to bilateral polycystic kidneys, who had undergone hemodialysis three times a week for 5 years, presented with hematemesis in December 2004. Based on the diagnosis of gastric cancer with lymph node metastases, surgery was performed. On the 15th postoperative day, the patient was treated with chemotherapy using paclitaxel. Paclitaxel was administered at a dose of 60 mg/m2 as a 1 h iv infusion in 250 mL of saline. Hemodialysis was started 1 h after the completion of the paclitaxel infusion and was performed for 3 h. Paclitaxel was administered weekly on d 1, 8, and 15 on a 28-d cycle. The maximum plasma concentration of paclitaxel was 1390μg/L. The area under the curve of paclitaxel was 4398.6μg·h/L Grade 2 leukopenia was encountered during the first cycle. The plasma concentrations of paclitaxel from 6 to over 24 h after the infusion were 0.01 to 0.1μmol/L in our patient, and these concentrations have been shown to be effective on inhibiting the growth of gastric cancer cells without producing adverse side effects in the patient. The plasma concentration of paclitaxel was not influenced by hemodialysis. We conclude that the pharmacokinetics of paclitaxel is not altered in a patient with renal failure, and that weekly paclitaxel is a suitable treatment regimen for hemodialysis patients with advanced gastric cancer.     

Advanced gastric cancer associated with DIC successfully treated with 5-FU and cisplatin: a case report

We report a case of advanced gastric cancer complicated by disseminated intravascular coagulation successfully treated with chemotherapy consisting of 5-fluorouracil and cisplatin. The patient was a 53-year-old woman who complained of loss of appetite, weight loss, and low back pain. Based on the laboratory data, a diagnosis of disseminated intravascular coagulation was made. Gastroscopy revealed gastric carcinoma (Borrmann type 3) that was continuously bleeding, and chest computed tomography showed a solitary lung metastasis and bilateral pleural effusion. Bone scintigraphy revealed multiple bone metastases. Accordingly, we made a diagnosis of stage IV gastric cancer complicated by disseminated intravascular coagulation. We selected the 5-fluorouracil and cisplatin combination chemotherapy for treatment and obtained the patient's consent. After two cycles of the 5-fluorouracil and cisplatin therapy, the bleeding symptoms improved and the disseminated intravascular coagulation process was successfully controlled. We concluded that disseminated intravascular coagulation caused by gastric cancer may be improved when the primary cancer and its metastases are brought under control by treatment with FP combination chemotherapy.     

Hepatic sinusoidal obstruction associated with S-1 plus cisplatin chemotherapy for highly advanced gastric cancer with paraaortic lymph node metastases: report of a case

A 56-year-old man who was diagnosed with gastric cancer with multiple paraaortic lymph node metastases was treated with S-1 plus cisplatin. The spleen gradually enlarged during the therapeutic courses. After the 6th course of therapy, the primary gastric lesion and paraaortic lymphadenopathies disappeared. He underwent a curative resection, including a distal gastrectomy with regional and paraaortic lymph node dissections. Irregularly distributed congestion of the liver was noted during the surgery. Histological examinations revealed residual cancer cells in 3 regional lymph nodes and no cancer cells in the primary site and paraaortic lymph nodes. Hepatic sinusoidal obstruction syndrome (SOS) was also confirmed histologically. This is the first report of a case with SOS after S-1 plus cisplatin therapy. S-1 plus cisplatin therapy can cause SOS, although it is a promising preoperative chemotherapy for highly advanced gastric cancer.     

Combined S-1 and cisplatin preoperative chemotherapy for patients with advanced gastric cancer: report of five cases

BACKGROUND/AIMS: A high response rate with acceptable toxicities is required in the setting of neoadjuvant chemotherapy. Five cases (3 stage IV, 2 stage IIIb) of advanced gastric cancer were successfully treated by neoadjuvant chemotherapy consisting of a combination of S-1 and cisplatin. METHODOLOGY: All 5 patients were men younger than age 60, with no severe complications. S-1 was administered orally (80 mg/m2/day) twice daily for 21 consecutive days, and cisplatin (60 mg/m2) was infused over 2 hours on day 8 with hydration. This schedule was repeated every 5 weeks. After each cycle, the clinical response evaluation was performed with endoscopy, barium meal, and spiral CT scan. Surgery was carried out about 3 weeks after chemotherapy. RESULTS: All patients were responders (100%) after one or two cycles. However, there was no patient with either complete response, or down-staging. Toxicities, according to the WHO criteria, were very mild and none required treatment. Postoperatively one patient died of aspiration pneumonia unrelated to the chemotherapy. The others were discharged within 3 weeks after operation without complications. CONCLUSIONS: S-1 plus cisplatin seems safe and effective as neoadjuvant chemotherapy in advanced gastric cancer patients.     

Non-platinum-based chemotherapy for treatment of advanced gastric cancer:5-fluorouracil,taxanes,and irinotecan

Despite numerous advances in treatment options,advanced gastric cancer(AGC)remains a major public health issue and the leading cause of cancer-related deaths.Cisplatin is one of the most effective broadspectrum anticancer drugs for AGC and a doublet combination regimen of either cisplatin-based or 5-fluorouracil(5FU)-based chemotherapy is generally used for treatment of patients with AGC.However,there is still no consensus on the best regimen for treating AGC.Recently,various new chemotherapeutic agents,including oral 5FU,taxanes,and irinotecan,have been identified as improving the outcomes for AGC when used as a single agent or in combination with nonplatinum chemotherapy.Nonetheless,it is still unclear whether non-platinum-based chemotherapy is a viable treatment option for patients with AGC.Accordingly,this review focuses on the efficacy and tolerability of non-platinum-based chemotherapy for patients with AGC.     

Phase Ⅱ study of protracted irinotecan infusion and a low-dose cisplatin for metastatic gastric cancer

AIM: To test protracted irinotecan infusion plus a low-dose cisplatin in this Phase II trial to decrease its toxicity. METHODS: The eligibility criteria were: (1) histologically proven measurable gastric cancer; (2) performance status of 0 or 1; (3) no prior chemotherapy or completion of prior therapy at least 4 wk before enrollment; (4) adequate function of major organs; (5) no other active malignancy; and (6) written informed consent. The regimen consisted of irinotecan (60 mg/m(2)) on d 1 and 15 by 24-h infusion and cisplatin (10 mg/m(2)) on d 1, 2, 3, 15, 16, and 17. Treatment was repeated every 4 wk. RESULTS: Thirty-one patients were registered between April 2000 and January 2001. The response rate for all 31 patients, 20 patients without prior chemotherapy, and 11 patients with prior chemotherapy was 52% (16/31), 60% (12/20), and 36% (4/11), respectively. The median survival time was 378 d. The median number of courses given to all patients was 2. Grade 4 neutropenia occurred in 11 (35%) patients, while grade 3 to 4 diarrhea or nausea occurred in 1 (3%) and 3 (10%) patients, respectively. Fatigue was minimal as grade 1 fatigue was found only in 3 (10%) patients. Other adverse events were mild and no treatment-related deaths occurred. CONCLUSION: This regimen showed a high level of activity and acceptable toxicity in patients with metastatic gastric cancer.     

Phase Ⅱ study of protracted irinotecan infusion and a low-dose cisplatin for metastatic gastric cancer

AIM: To test protracted irinotecan infusion plus a lowdose cisplatin in this Phase Ⅱ trial to decrease its toxicity.METHODS: The eligibility criteria were: (1) histologically proven measurable gastric cancer; (2) performance status of 0 or 1; (3) no prior chemotherapy or completion of prior therapy at least 4 wk before enrollment; (4)adequate function of major organs; (5) no other active malignancy; and (6) written informed consent. The regimen consisted of irinotecan (60 mg/m2) on d 1 and 15 by 24-h infusion and cisplatin (10 mg/m2) on d 12 2, 3,15, 16, and 17. Treatment was repeated every 4 wk.RESULTS: Thirty-one patients were registered between April 2000 and January 2001. The response rate for all 31 patients, 20 patients without prior chemotherapy, and 11 patients with prior chemotherapy was 52% (16/31),60% (12/20), and 36% (4/11), respectively. The median survival time was 378 d. The median number of courses given to all patients was 2. Grade 4 neutropenia occurred in 11 (35%) patients, while grade 3 to 4 diarrhea or nausea occurred in 1 (3%) and 3 (10%) patients,respectively. Fatigue was minimal as grade 1 fatigue was found only in 3 (10%) patients. Other adverse events were mild and no treatment-related deaths occurred.CONCLUSION: This regimen showed a high level of activity and acceptable toxicity in patients with metastatic gastric cancer.     

Phase Ⅱ study of protracted irinotecan infusion and a low-dose cisplatin for metastatic gastric cancer

AIM: To test protracted irinotecan infusion plus a lowdose cisplatin in this Phase Ⅱ trial to decrease its toxicity.METHODS: The eligibility criteria were: (1) histologically proven measurable gastric cancer; (2) performance status of 0 or 1; (3) no prior chemotherapy or completion of prior therapy at least 4 wk before enrollment; (4)adequate function of major organs; (5) no other active malignancy; and (6) written informed consent. The regimen consisted of irinotecan (60 mg/m2) on d 1 and 15 by 24-h infusion and cisplatin (10 mg/m2) on d 12 2, 3,15, 16, and 17. Treatment was repeated every 4 wk.RESULTS: Thirty-one patients were registered between April 2000 and January 2001. The response rate for all 31 patients, 20 patients without prior chemotherapy, and 11 patients with prior chemotherapy was 52% (16/31),60% (12/20), and 36% (4/11), respectively. The median survival time was 378 d. The median number of courses given to all patients was 2. Grade 4 neutropenia occurred in 11 (35%) patients, while grade 3 to 4 diarrhea or nausea occurred in 1 (3%) and 3 (10%) patients,respectively. Fatigue was minimal as grade 1 fatigue was found only in 3 (10%) patients. Other adverse events were mild and no treatment-related deaths occurred.CONCLUSION: This regimen showed a high level of activity and acceptable toxicity in patients with metastatic gastric cancer.     

中药胃宁颗粒联合化疗防治胃癌复发转移的临床分析

目的:研究胃宁颗粒联合化疗对胃癌复发移的防治作用.方法:160例术后胃癌患者随机分为治疗组80予胃宁颗粒配合化疗,对照组80例予单纯化疗.观察治疗前后局部复发及远处转移情况,血液流变学指标血浆黏度、全血黏度、血沉方程(K值)、红细胞聚集指数、纤维蛋白原,金属蛋白酶-9(MMP-9)、血管内皮生长因子(VEGF)含量、复发转移病灶大小,复发转移者生活质量的变化.结果:治疗组1年后复发转移率22.22%,对照组为32.22%,两组比较差异有显著性意义(P＜0.05);治疗组治疗后血浆黏度、全血黏度、纤维蛋白原、MMP-9、VEGF含量与对照组相比显著降低(1.26±0.13 mPa·s vs 1.75±0.11 mPa·s,8.73±1.98 mPa·s vs 20.56±2.31 mPa·s,2.15±0.16 vs 3.85±0.41,135.46±22.16 μg/L vs 186.23±31.56 μg/L,102.46±18.43 vs 176.43±21.56,P＜0.05或P＜0.01);治疗组对复发转移灶大小抑制率为30.00%,对照组为17.85%,两组比较差异有显著性意义(P＜0.05);治疗组对复发转移患者生活质量改善显著优于对照组(P＜0.01).结论:胃宁颗粒和化疗药物联用,具有一定的协同作用,可以提高疗效,改善患者生存质量,其机制可能与改善微循环、降低MMP-9、VEGF含量有关.     

Secondary acute promyelocytic leukemia following chemotherapy for gastric cancer: A case report

Therapy-related acute myeloid leukemia(t-AML) refers to a heterogeneous group of myeloid neoplasms that develop in patients following extensive exposure to either cytotoxic agents or radiation. The development of t-AML has been reported following treatment of cancers ranging from hematological malignancies to solid tumors; however, to our knowledge, t-AML has never been reported following treatment of gastric cancer. In this study, we report the development of t-acute promyelocytic leukemia in a cT 4N1M0 gastric cancer patient after an approximate 44 mo latency period following treatment with 4 cycles of oxaliplatin(OXP)(85 mg/m2 on day 1) plus capecitabine(1250 mg/m2 orally twice daily on days 1-14) in combination with recombinant human granulocyte-colony stimulating factor treatment. Karyotype analysis of the patient revealed 46,XY,t(15;17)(q22;q21)[15]/46,idem,-9,+add(9)(p22)[2]/46,XY[3], which, according to previous studies, includes some “favorable” genetic abnormalities. The patient was then treated with all-trans retinoic acid(ATRA, 25 mg/m2/d) plus arsenic trioxide(ATO, 10 mg/d) and attained complete remission. Our case illuminated the role of certain cytotoxic agents in the induction of t-AML following gastric cancer treatment. We recommend instituting a mandatory additional evaluation for patients undergoing these therapies in the future.     

Neoadjuvant chemotherapy with paclitaxel plus cisplatin before radical surgery for locally advanced cervical cancer during pregnancy: A case series and literature review

Rationale:Despite the development of human papillomavirus vaccines and significant improvement in cervical cancer screening over the past few years, cervical cancer remains the fourth most common cancer in women of childbearing age after breast cancer, melanoma, and thyroid cancer.Patient concerns:In this case report, the patients are all cervical cancer with stage IB2 and IB3 during pregnancy, the management constitutes a major medical challenge related to the impact of treatment on both maternal and fetal outcomes. Neoadjuvant chemotherapy (NACT) is an innovative option for cervical cancer patients with stage IB2 and IB3 before cesarean delivery and radical hysterectomy, and many chemotherapeutic agents are available, cisplatin plus paclitaxel yielded good maternal and fetal outcomes to the authors’ knowledge.Diagnoses:Masses were discovered in the cervix of 4 pregnant women with a history of vaginal bleeding. Biopsy examination of the masses revealed cervical carcinoma, which was staged in accordance with the International Federation of Gynecology and Obstetrics (i.e., FIGO) system.Interventions:The patients were treated with paclitaxel plus cisplatin, followed by cesarean delivery and radical hysterectomy.Outcomes:The 4 patients were treated successfully, with no recurrence during follow-up periods of 14 to 56 months, and all of the children were doing well with no anomalies.Lessons:Although further data are required, in pregnant women with invasive cervical cancer, NACT with cisplatin plus paclitaxel followed by cesarean delivery and radical hysterectomy was a practical treatment option.     

紫杉醇顺铂方案联合同步放疗治疗顺铂依托泊苷化疗不敏感局限期小细胞肺癌的临床疗效

目的探讨紫杉醇顺铂联合同步放疗对顺铂依托泊苷(EP)不敏感局限期小细胞肺癌的治疗作用。方法 EP两周期化疗结束2 w后评估为无变化和疾病进展的患者为研究对象,在知情同意下随机分为继用EP方案化疗联合同步放疗组(观察组)和改用紫杉醇顺铂联合同步放疗组(对照组)。观察两组的毒副作用,评估治疗结束后4 w的近期临床有效率(RR),以疾病无进展生存时间(PFS)为随访终点。结果观察组的RR为37.5%(6/16),对照组为76.5%(13/17),两组差异显著。中位PFS:观察组为6.0个月,对照组为12.0个月,两组差异显著。两组骨髓抑制、放射性食管炎及放射性肺炎等不良反应无统计学差异。结论紫杉醇顺铂联合同步放疗对EP两周期化疗不敏感局限期小细胞肺癌有效。     

Double cancer (lung and colon cancer) that showed complete remission with irinotecan and cisplatin combined chemotherapy

We report a rare case of double (colon and lung) cancer which showed complete remission with chemotherapy with irinotecan (CPT-11) and cisplatin (CDDP). The patient was a 67-year-old man who was diagnosed as having double cancer (stage IIIb pulmonary adenocarcinoma and stage 0 [or 1] well-differentiated adenocarcinoma of the ascending colon). Two courses of chemotherapy (CPT-11, 60 mg/m², days 1 and 8; CDDP, 30 mg/m², days 1 and 8) were performed. The combination therapy of CPT-11 and CDDP was very effective. In Japan, there have been few published reports describing the use of CPT-11 for the treatment of gastrointestinal cancer. We think that the use of CPT-11 in gastrointestinal cancer is promising. Received: August 18, 1999 / Accepted: March 24, 2000     

Neoadjuvant chemotherapy combining docetaxel, cisplatin and S-1 in gastric cancer with para-aortic lymph node metastases: report of five cases

We report on five patients with a median age of 56 years (range, 53-68 years) who were diagnosed as advanced gastric cancer with para-aortic lymph node metastases, determined by gastrofiberscope and abdominal spiral computed tomography. These patients received intravenous docetaxel (30 mg/m2) and cisplatin (30 mg/m2) on day 1, 15 and oral S-1 (40 mg/m2 bid) on days 1-14 every 4 weeks. After two cycles of neoadjuvant chemotherapy, all patients received total gastrectomy with D2 lymphadenectomy plus para-aortic lymph nodes dissection. No patient revealed hematological or non-hematological toxicities associated with the chemotherapy (more than grade 2). The postoperative courses were uneventful without major surgery-related complications. Pathological complete response was confirmed one patient in primary lesion and three patients in metastatic lymph nodes including para-aortic lymph nodes. All of five patients are alive without recurrence (median: 36 months, 21-46 months). Thus, neoadjuvant chemotherapy described here may be rather promising regimen for advanced gastric cancer with para-aortic lymph node metastases, considering its low grade toxicities and pathological responses.     

Second-line chemotherapy with paclitaxel and doxifluridine after failure of S-1 in elderly patients with unresectable advanced or recurrent gastric cancer

Purpose  

There is no standard second-line treatment for patients with unresectable advanced or recurrent gastric cancer (URGC) in the event that first-line treatment fails. Moreover, the benefits of second-line chemotherapy in elderly patients remain uncertain. The aim of this study was to identify the benefits of the second-line paclitaxel (PTX) plus doxifluridine (5′-DFUR) regimen for URGC in elderly patients in comparison to nonelderly patients.     

Second-line combination chemotherapy of oral S-1 with cisplatin and irinotecan for colorectal cancer resistant to 5-FU

BACKGROUND/AIMS: A phase I clinical trial has been planned to determine the recommended dose and to assess the safety and efficacy of combination chemotherapy of S-1 with cisplatin and irinotecan (SCI regimen) as a second-line treatment in 5-fluorouracil (5-FU) resistant colorectal cancer (CRC). METHODOLOGY: Patients with unresectable recurrent or metastatic CRC were enrolled in this study for second-line treatment. On an outpatient basis, the patients received a treatment SCI regimen comprising S-1 oral administration for 28 days followed by withdrawal for 2 weeks, plus cisplatin and irinotecan were administered on days 1, 8, 15 and 22 by intravenous injection. These courses were repeated every 6 weeks. Starting doses were 70 mg/m2 S-1, 6 mg/m2 Cisplatin, and 60 mg/m2 Irinotecan. RESULTS: A total of 29 patients was enrolled. Dose-limiting toxicities were fatigue, nausea, and leucopenia. Twenty-three patients at recommended dose were evaluable for treatment response. The response rate was 21.7% (5 partial responses, 13 stable diseases, and 5 progressive diseases). The median progression-free survival rate was 4.3 months; the median survival time was 9.6 months. CONCLUSIONS: The SCI regimen is feasible in an outpatient setting and should be considered as second-line chemotherapy for patients with 5-FU resistant CRC.