Effect of cis-diammine dichloroplatinum, vindesine sulfate combination chemotherapy for advanced esophageal carcinoma

Eleven patients with advanced squamous cell carcinoma of the esophagus were treated with a two-drug combination of cis-diammine dichloroplatinum and vindesine sulfate at Saitama Cancer Center between July 1982 and September 1983. Median age was 71 years old (range: 47-48) and 8 patients were greater than 70 years old. Median performance status was 3 (range: 1-4) by Koyama -Saito Criteria. Male female ratio was 6:5. Of the 11 patents, three obtained partial response (27.3%), lasting 8 weeks, 20 weeks+, and 42 weeks-, respectively, and three patients had minor response (27.3%). The major toxic effects including myelosuppression, nausea and vomiting were in general manageable.     

Combination chemotherapy of esophageal carcinoma using cisplatin, vindesine, and bleomycin

Sixty-one patients with epidermoid carcinoma of the esophagus have been treated with a three drug combination of cisplatin, vindesine, and bleomycin. Of 53 patients currently evaluable for response, 29 (55%) have had partial remissions: 7/16 with metastatic, and 22/37 with local-regional disease. The median duration of response in metastatic patients is eight months. Of 28 patients treated preoperatively, 23 (82%) had resectable disease. The major toxicities seen were nephrotoxicity and myelosuppression. Cisplatin, vindesine and bleomycin is an effective combination in the treatment of esophageal carcinoma. Effects on long-term survival cannot yet be evaluated.     

Combination chemotherapy with cis-dichlorodiammineplatinum (11) (CDDP) and bleomycin BLM in advanced esophageal carcinoma

Five patients with advanced carcinoma of the esophagus were treated with a combination chemotherapy employing CDDP and BLM. One cycle of chemotherapy consisted of CDDP, 50 mg/m2, on day 1 and BLM, 15 mg/patient on days, 1, 7 and 14. Two partial remission and 2 minor responses were obtained. Overall response rates, ths, were 80%. The most adverse effect was nausea. No significant elevation in the serum creatinine or BUN was recognized. Furthermore, the method of CDDP administration was studied on the serum level by 15 minutes' infusion and by 24 hours continuous infusion. The CDDP levels in the serum and tissue were determined by flameless atomic absorption spectrophotometry. The CDDP level in the serum by 15 minutes' infusion was higher than that by 24 hours continuous infusion. These results suggest that combination chemotherapy with CDDP and BLM may be a useful method for the treatment of advanced esophageal carcinoma.     

Combination chemotherapy with cis-diamminedichloroplatinum (CDDP) and other anticancer agents for patients with advanced esophageal cancer

Combination chemotherapy with cis-diamminedichloroplatinum (CDDP) and other anticancer agents was performed in patients with advanced esophageal cancer. From July 1982 to September 1984, 16 patients were entered into this study and divided into two regimens. In regimen I, 5 patients were treated with a daily dose of 20 mg CDDP and 10 mg Peplomycin for five consecutive days and 10 mg Mitomycin C on the first day. This course was repeated 2 or 3 times every 4 weeks. As for evaluation, 1 PR (20%) and 4 NC (80%) were observed. In regimen II, nine patients were treated with daily doses of 25 mg CDDP and 2 mg Vindesine for 5 consecutive days, a course which was repeated every 4 weeks. As for evaluation, 1 CR (9%), 1 PR (9%), 4 MR (36%), 2NC (18%), and 3 PD (27%) were observed. Major side effects were renal failure, bone marrow suppression, nausea and vomiting, which were mostly transient. However, more severe bone marrow suppression was observed in regimen I composed with regimen II.     

Combination chemotherapy for advanced urothelial-tract carcinoma

Between December 1982 and November 1990, 31 patients with advanced urothelial carcinoma were treated with one of two combination chemotherapy regimens. A total of 20 patients were treated with 3 mg/m² mitomycin C and 300 mg/m² cyclophosphamide given intravenously every 10–14 days and with 180 mg/m² 5-fluorouracil (5-FU) given intravenously every day for as long as possible (CF-Mito regimen). After the patient had been discharged from the hospital, the same treatment with CF-Mito was performed except that 180 mg/m² 5-FU was replaced by 400 mg/m² UFT (a mixture of tegafur and uracil) given orally. A total of 11 patients whose tumor had relapsed during the first-line treatment were given 60 mg/m² cisplatin, 40 mg/m² Adriamycin, and 40 mg/m² methotrexate intravenously every 28 days (PAM regimen). In all, 20 patients received 4–44 (mean, 9.7) courses of CF-Mito over a period of 1.5–24 (mean, 5.3) months. The results obtained in these 20 patients with evaluable lesions included no complete remission (CR), 4 partial remissions (PRs), 9 cases of stable disease (SD), and 7 cases of progressive disease (PD). The PR duration was 1.5–22 (mean, 7.5) months. The side effects encountered in this group included anorexia, nausea, vomiting, myelosuppression, diarrhea, stomatitis, liver damage, and heart failure. In all, 11 patients received 3–7 (mean, 4.1) courses of PAM over a period of 3–14.5 (mean, 5.2) months. All 11 patients had evaluable lesions, and their responses included no CR, 5 PRs, 3 cases of SD, and 3 cases of PD. The Pr duration was 1–3 (mean, 1.6) months. The side effects encountered in this group included anorexia, nausea, vomiting, myelosuppression, heart failure, and hair loss.Presented at the 4th International Conference on Treatment of Urinary Tract Tumors with Adriamycin/Farmorubicin, 16–17 November 1990, Osaka, Japan     

A phase II study of capecitabine and cisplatin (XP) as first-line chemotherapy in patients with advanced esophageal squamous cell carcinoma

Purpose The combination of 5-fluorouracil (5-FU) and cisplatin (FP) remains the mostly used regimen for metastatic esophageal squamous carcinoma. This phase II study assessed the efficacy and safety of capecitabine/cisplatin (XP) as a first-line chemotherapy in a homogenous cohort of patients with metastatic or recurrent esophageal squamous cell carcinoma. Materials and methods Patients received 60 mg/m² of cisplatin intravenously (IV) on day 1 and capecitabine 1,250 mg/m²/dose orally twice a day on days 1–14. Treatment cycles were repeated every 3 weeks until the documented disease progression, unacceptable toxicity, or patient’s refusal. Immunohistochemical studies against thymidylate synthase (TS) and thymidine phosphorylase (TP) were performed to seek predictive markers for treatment response. Results Between December 2003 and March 2006, 45 patients entered the study. All patients had histologically proven squamous cell carcinoma of the esophagus. The overall response rate (ORR) was 57.8% (95% CI, 43.3–72.2) with 0 CR and 26 PRs. The median duration of response in responders was 4.6 months (1.0–15.6 months). With a median follow-up duration of 25.7 months (10.8–42.6 months), the median time to progression was 4.7 months (95% CI, 2.5–7.0) and the median survival time was 11.2 months (95% CI, 8.5–13.9). Common grade 3 or 4 non-hematological adverse events were anorexia (18/191, 9.4%), fatigue (9/191, 4.7%), constipation (6/191, 3.1%), hand-foot syndrome (6/191, 3.1%) and diarrhea (4/191, 2.1%). The most common grade 3 or 4 hematological adverse events were neutropenia (33/191, 17.3%), followed by leucopenia (11/191, 5.8%), anemia (2/191, 1.0%) and thrombocytopenia (1/191, 0.5%). There was no treatment-related death. Neither TS nor TP showed predictive value for treatment response. Conclusion The XP regimen demonstrated a promising antitumor activity in metastatic esophageal squamous cell carcinoma, which may potentially replace the FP regimen.     

后程加速超分割放疗结合化疗治疗96例中、晚期食管癌

目的 :评价后程加速超分割放疗结合化疗治疗中、晚期食管癌的临床疗效。方法 :1 76例中、晚期食管癌 ,根据不同的治疗方法分为两组 :单纯根治性放射治疗组 (单放组 )和后程加速超分割放疗结合化疗组 (综合放化组 )。单放组共 80例 ,采用常规设野放疗。照射剂量为 64～ 70Gy。综合组共 96例 ,放射方法均为前 2 3疗程常规放疗 ,每次2 .0Gy,共 40Gy ;后 1 3疗程缩野改为加速超分割放射治疗 ,每天 2次 ,1 .3Gy 次 ,共 2 4～ 30Gy;化疗采用PF方案[顺铂 (DDP) 2 0mg 次静脉点滴 ,第 1～ 5天 ;氟尿嘧啶 (5 FU) 750mg 次静脉点滴 ,持续 8小时以上 ,第 1～ 5天 ,2 8天为 1周期 )。两组均随访 5年 ,失访 1 7例 ,随访率 90 .3 %。结果 :原发灶的近期疗效综合放化组好于单放组 ,两组间差异有显著性 (P <0 .0 5) ;锁骨上淋巴结转移灶的近期疗效两组间差异无显著性 (P >0 .0 5) ;综合放化组与单放组一、三、五年生存率分别为 69.8%、51 .1 %、2 9.2 %和 46 .3 %、2 1 .3 %、1 1 .3 % ,综合组疗效明显好于单放组 ,一、三年生存率两组间差异有显著性 (P <0 .0 5) ,但五年生存率两组间差异无显著性 (P >0 .0 5)。局部控制率综合放化组明显高于单放组 (P <0 .0 5) ,远处转移率两组相近。综合组的急性放射性气管炎和急性     

Cis-diamminedichloroplatinum(II) chemotherapy in advanced pancreatic carcinoma

The effect of cis-diamminedichloro platinum (II) (CDDP) was evaluated in 14 patients with advanced pancreatic carcinoma. Prior chemotherapy was done in 7 cases and the remaining 7 were fresh cases. The drug was given at a dose of 80 mg/m2 I.V. every 3 weeks, with hydration and mannitol diuresis. Four cases out of 14 showed no change, while the remaining 10 cases showed progressive disease. The response rate was 0%. Most of the patients who showed myelosuppression had received prior chemotherapy. Non-hematologic toxicity occurred in 9 patients (64%) and consisted of nausea in 9, vomiting in 7 and anorexia in 9. Values of serum creatinine and BUN were transiently elevated.     

Combination chemotherapy with hexamethylamine (Hexalen, Altretamine, Hexastat) and sarcolysine in advanced ovarian carcinoma

Combination chemotherapy with hexamethylmelamine (hexalen, altretamine, hexastat), 100 mg, thrice a day, per os, 14 days (out of a 28-day course) and sarcolysin, 15 mg, per os, during the first 5 days of the course, was received by 24 patients with primary advanced tumors of the ovaries, prior to or after cytoreductive surgery. Total apparent response to chemotherapy among 19 patients of the study group was 47.2%, clinically significant (plus stabilization)--94.5%, without significant untoward side-effects (vomiting--19%; leukopenia degree II-III--33% and thrombocytopenia--19%). The drug proved an active component of combination therapy for advanced ovarian carcinoma.     

Combination chemotherapy for advanced bilharzial bladder carcinoma

BACKGROUND:: Carcinoma of the bilharzial bladder, the most common cancerin Egyptian patients has been, until recently, largely treatedby surgery. We have studied the activity of a series of singleagents in phase II trials and identified a number of activeagents. Here we report the results of a trial in which therapeuticcombinations of the most active agents were administered inalternating cycles to patients who had never received chemotherapy. PATIENTS AND METHODS:: The study included 30 patients with histologically proven inoperable(20), recurrent (5, 2 of whom subsequently developed metastases),or metastatic disease (5). There were 27 males and 3 females,with a median age of 48.5 years (range 29–65 years). Fourteenpatients had squamous cell carcinoma, 12 had transitional cellcarcinoma, 2 had adenocarcinoma, and the remaining 2 had undifferentiatedcarcinoma. Chemotherapy consisted of epidoxorubicin (120 mg/sqm i.v. d1)and vincristine (1.4 mg/sqm i.v., days 1 and 8) alternatingwith etoposide (100 mg/sqm i.v. infusion over 1 hour, days 1to 5) and ifosfamide (1800 mg/sqm i.v. infusion over 2 hours,days 1 to 5). Mesna was given as a uroprotector at 40% of theifosfamide dose at 0, 4, and 8 hours after the ifosfamide infusion.Courses were repeated every 3–4 weeks. RESULTS:: Among the 22 evaluable patients, 8 (36.5%) had a partial andone (4.5%), a complete response, giving a response rate of 46%.Three more patients had responses that were less than a partialremission, and 6 patients showed disease stabilisation on chemotherapy.Toxicities were tolerable and consisted mainly of myelosuppression. Results were further analysed in relation to pathologic subtype,disease status at the start of chemotherapy, and the delivereddose intensity. No relationship was found between any of theseparameters and response to therapy. CONCLUSION:: Advanced bilharzial bladder cancer is relatively sensitive tocombination chemotherapy, but complete remission and prolongedsurvival is rare in this subgroup of patients with advanceddisease. Further studies will be needed to determine the relativeefficacy of single agents and drug combinations. bilharziasis, bladder cancer, chemotherapy     

Simultaneous chemotherapy and radiotherapy with escalating doses of chemotherapy in patients with advanced esophageal carcinoma.

From January 1992 to January 1995, 39 patients were diagnosed with esophageal carcinoma at the Department of Veterans Affairs Medical Center in Washington, D.C. All of the patients were men aged 44 to 78, and the median age was 66. Staging included a physical examination, serum chemistries, barium swallow, endoscopy with biopsy, and computed tomographic scans of the chest and abdomen. Seven patients were ineligible for the study because they had poor performance status, refused treatment, or received treatment at another medical center. All the patients treated had a performance status of 1 to 2. In 1992, 15 patients received 400 mg/m2/d 5-fluorouracil; in 1993, eight patients received 500 mg/m2/d 5-fluorouracil; and in 1994, nine patients received 600 mg/m2/d 5-fluorouracil as a continuous intravenous infusion during radiotherapy, which consisted of 60 Gy over 6 to 8 weeks. The complete response rates were 26%, 25%, and 22% for 1992, 1993, and 1994, respectively. The median survival was 11 months, 14 months and 9 months for those same years, respectively. The major toxicities were hematologic. Three patients died of pneumonia during treatment. Simultaneous chemotherapy and radiotherapy is an effective mode of therapy for localized esophageal carcinoma. However, escalating doses of chemotherapy did not increase the complete response rate.     

化放疗序贯治疗局部晚期食管癌的疗效分析

目的观察比较局部晚期食管癌放疗加化疗和单纯放疗的疗效.方法 148例局部晚期食管癌患者随机分为两组:化放组76例,单放组72例.化疗方案:CF 100～200 mg,d1～5;5-Fu每日500 mg/m2,d1～5;CDDP每日25mg/m2,d1～3.化疗结束后3～7 d开始放射治疗,放射治疗采用8 MV X线照射,先设前后野DT 40～44 Gy/4.0～4.4周后,即重复上述化疗方案,化疗完成后再缩野避开脊髓等中心放疗DT 24～26 Gy/2.4～2.6周.结果化放组的1,3,5年生存率分别为73.7%、31.5%和15.8%,单放组分别为61.1%、16.7%和5.5%.两组间3,5年生存率比较差异有显著性(P＜0.05).化放组毒副反应较重.两组的死亡原因主要为局部复发,其次为远处转移,差异无显著性(P＞0.05).结论以5-Fu CDDP CF 联合诱导化疗加放射治疗局部晚期食管癌,可以提高疗效,延长生存期,虽毒副反应略增加,但患者均可耐受.     

Analysis of mutations induced in the SUP4-o gene of Saccharomyces cerevisiae by cis-diammine dichloroplatinum(II)

A collection of 196 mutations induced in the SUP4-o gene of yeast by treatment with cis-diammine dichloroplatinum(II) (cis-DDP) was characterized by DNA sequencing. All possible types of base pair substitution were identified as well as deletions, insertions and double mutations. Base pair changes at G.C sites predominated and were distributed throughout the gene. The majority of substitutions occurred at 5'-GG-3' and 5'-GA-3' sequences, potential sites of cis-DDP adducts. However, mutations were also detected at a number of other DNA sequences where cis-DDP has been found to bind in vitro or form adducts in vivo including 5'-AA-3', 5'-AG-3', 5'-GNG-3' and 5'-AAA-3'. The site specificity of cis-DDP mutagenesis argues that some of these sequences are significant targets for the induction of mutation in vivo despite the fact that they were considered to be weak binding sites for cis-DDP in vitro. In addition, the distribution of the substitutions within the SUP4-o gene indicates that DNA sequence context influences cis-DDP mutagenesis in vivo. Finally, our results suggest that intrastrand cross-links formed by cis-DDP might facilitate the gain or loss of single base pairs by stabilizing strand misalignments that template these events.     

Phase II trial of neoadjuvant chemotherapy with docetaxel,nedaplatin, and S1 for advanced esophageal squamous cell carcinoma

Although standard chemotherapy for esophageal cancer patients is fluorouracil and cisplatin, the prognosis is still unsatisfactory. A new therapeutic regimen combining docetaxel, cisplatin, and 5‐fluorouracil was recently developed to improve both local and distant tumor control. We developed a new regimen of docetaxel, nedaplatin, and S1 (DGS) and previously reported the recommended dose in a phase I dose‐escalation study. We then undertook a phase II study of DGS for advanced esophageal squamous cell carcinoma. Patients with clinical stage IB/II/III disease were eligible. Patients received two courses of chemotherapy: docetaxel 35 mg/m² with nedaplatin 40 mg/m² on day 8, 80 mg/m² S1 on days 1–14, and 2 weeks off. After completion of chemotherapy, patients underwent esophagectomy. The primary endpoint was the completion rate of protocol treatment (completion of two courses of preoperative chemotherapy and R0 surgery [no residual tumor]). We enrolled 32 patients. The completion rate of protocol treatment was 96.9%. During chemotherapy, the most common grade 3 or 4 toxicity was neutropenia (25.0%). No treatment‐related deaths were observed, and the incidence of operative morbidity was tolerable. The overall response rate after chemotherapy was 83.3%. This DGS regimen was well tolerated and highly active. This trial is registered with the University Hospital Medical Information Network (UMIN ID: 000014626).     

Combination chemotherapy with cis-diammine-di-chloro-platinum (II) and bleomycin in advanced head and neck cancer

Combination chemotherapy of cis-diammine dichloro platinum (II) (CDDP) and bleomycin was given to 10 patients with advanced squamous cell carcinoma of the head and neck. Nine patients had received prior radical radiotherapy, 2 had major ablative surgical procedures, and one had been previously treated with chemotherapy. Responses were as follows (duration in months): 2 CRs (4,6+), 2 PRs (1.5,1.5), and 2 minors. Vomiting related to CDDP was observed in 5 patients, nephrotoxicity and hypocalcemia in one patient were also observed.     

Combination chemotherapy with cis-platinum, adriamycin, mitomycin-C (PAM) in patients with advanced bladder cancer

Thirty patients with advanced bladder cancer received combination chemotherapy with cis-platinum, adriamycin and mitomycin C. Two patients (6.6%) responded completely and survived 24 and 30 months. Partial response was noted in 14 patients (46.6%) who had a median survival of 9.6 months. Eight patients (26.6%) had stable disease with a median survival of 5 months whereas in 6 patients (20%) their disease progressed with a median survival of 3 months. The amelioration of hematuria, regardless of response, was impressive. Nausea and vomiting were the commonest side effects. Myelotoxicity was mild and reversible. We conclude that PAM chemotherapy is effective and well tolerated in patients with advanced bladder cancer.     

Combination chemotherapy of advanced transitional cell carcinoma with cis-platinum, cyclophosphamide, adriamycin and 5-fluorouracil (CISCAF)

Ten patients with advanced transitional cell carcinoma were treated with the combination chemotherapy (CISCAF) consisting of cis-platinum (CDDP), cyclophosphamide (CPM), adriamycin (ADM) and 5-fluorouracil (5-FU). There were 8 males and 2 females with a median age of 57 years (range 33-76). Prior to this chemotherapy, all primary lesions were resected surgically; one patient received irradiation, one interferon. CDDP (15 mg/m2) with mannitol diuresis and ADM (7 mg/m2) were given daily for 5 days. CPM (200-300 mg/m2) was given on day one, and 5-FU (200-300 mg/m2) on day 2. Courses were repeated every 3-4 weeks for 3 courses and later every 2 months. All patients were evaluable for toxicity and 9 for response. There were 3 (33%) partial and 2 minor responses. Survival difference between responders (PR + MR) vs non-responders (NC + PD) was significant during the 30-120 days of observation, but not significant throughout the whole period (generalized Wilcoxon test). The overall toxicity due to chemotherapy was generally mild, except for one irreversible nephrotoxicity and one gastric hemorrhage treated surgically.     

局部晚期食管癌患者累及野照射联合化疗的疗效分析

目的分析局部晚期食管癌患者累及野照射联合化疗的失败模式及预后。方法回顾性分析2003-01-01-2009-01-01山东省肿瘤医院放疗科接受累及野放疗联合化疗的80例局部晚期食管癌患者,依据首次复发部位与治疗靶区,将失败模式分为照射野内复发、野外区域淋巴结复发和远处转移,并分析不同复发模式组的生存情况。结果治疗结束后80例患者治疗有效68例（85.00%）,达临床完全缓解（CR）19例（23.75%）,部分缓解（PR）49例（61.25%）。中位随访时间52.6个月（95%CI：46.1-56.7个月）,全组患者的中位生存时间（median survival time,MST）为14.4个月。共76例患者出现复发,其中野内复发43例（53.75%）,远处转移33例（41.25%）,野外区域淋巴结复发24例（30.00%）。有野内复发或远处转移的患者MST分别为14.2和13.2个月,均显著低于未出现者的17.4个月（P=0.01）和15.9个月（P〈0.001）,而出现野外区域淋巴结转移与未出现者MST均为14.5个月,差异无统计学意义,P=0.665。结论累及野放疗联合化疗治疗局部晚期食管癌,野内复发及远处转移为主要复发模式且影响生存,而野外区域淋巴结并未明显影响患者总生存期,其可行性有待多中心大样本前瞻性随机对照试验进一步证实。