Basaloid-Squamous Carcinoma of the Esophagus Treated by Preoperative Chemotherapy: Report of Two Cases

Basaloid squamous carcinoma (BSC) of the esophagus has been associated with a poor outcome after surgery. We herein report two patients with esophageal BSC treated by preoperative chemotherapy. Patient 1 was a 55-year-old man who presented with a tumor of the middle esophagus diagnosed as BSC. He was treated by chemotherapy using a combination of 5-fluorouracil (5-FU: 750 mg/m², 1st–5th day, 24-h continuous infusion) and cisplatin (CDDP: 75 mg/m², 1st day, drip infusion per 2 h) before surgery, because of lymph node metastases of the mediastinum and around the left gastric artery. Even though the metastatic nodes were reduced and an esophagectomy was performed, the patient died of recurrence 12 months after chemotherapy. Patient 2 was a 57-year-old man who demonstrated BSC of the esophagus with direct invasion to the discending aorta, who was treated by preoperative chemotherapy using the same regimen as that of patient 1. The esophageal tumor was reduced, and a curative esophagectomy was performed. The patient is now alive without recurrence 38 months after chemotherapy. In conclusion, preoperative chemotherapy using a combination of 5-FU and CDDP may thus be an effective treatment for patients with advanced BSC of the esophagus. Received: September 19, 2001 / Accepted: May 7, 2002 RID="*" ID="*" Reprint requests to: N. Koide     

Clinical evaluation of adjuvant chemoradiotherapy with CDDP, 5-Fu, and VP-16 for advanced esophageal cancer

Objectives

The aim of this study was to evaluate the efficacy of adjuvant chemoradiotherapy following surgery in patients with advanced esophageal cancer.

Subjects and Methods

We followed the cases of 57 such patients treated at our hospital, involving 19 who received adjuvant chemoradiotherapy (CR group), 19 who received radiotherapy alone (R group), and 19 who did received neither (N group). In the CR group, chemotherapy, consisting of cis-diaminodichloroplatinum (CDDP), 5-fluorouracil (5-FU), and etoposide (VP-16), was combined with radiotherapy was administered from 4 weeks after surgery. Concurrent radiotherapy was started at 3 weeks after esophagectomy. CDDP at 50 mg/m² was administered on days 1 and 7. 5-FU at 500 mg/m² and VP-16 at 60 mg/m² were administered on days 3, 4, and 5. Thirteen patients (68.4%) were treated with more than 2 cycles of chemotherapy combined with radiation.

Results

Side-effects of severe anorexia (grade 3) and leukocytopenia (<1900/μl) were observed in 47% and 39% of the patients, respectively. However no treatment-related death was observed. The 5-year-survival rate was 25.2%, 18.9%, and 15.8%, in the CR group, R group, and N group, respectively. The recurrence rate was 66.7% in the CR group, which was higher than in the matched control groups (46.2% in the N group and 54.5% in the R group), but with no a significant difference.

Conclusion

These results suggested that adjuvant chemoradiotherapy did not contribute to improvement in prognosis for these patients with advanced esophageal cancer.     

The role of neoadjuvant radiochemotherapy using low-dose fraction cisplatin and 5-fluorouracil in patients with carcinoma of the esophagus

OBJECTIVE: We clarified the role of neoadjuvant radiochemotherapy in patients with carcinoma of the esophagus and compared it to neoadjuvant chemotherapy. METHODS: We retrospectively examined 40 patients diagnosed with advanced thoracic esophageal carcinoma who underwent neoadjuvant therapy followed by esophagectomy between 1993 and 1999. We divided them into 2 groups: radiochemotherapy (17) and chemotherapy (23). Radiochemotherapy patients underwent 40 Gy radiation and low-dose fraction cisplatin (7 mg/body/day, 5 days a week x 4 weeks) and 5-fluorouracil (350 mg/body/day x 28 days). Chemotherapy patients received high-dose fraction cisplatin/5-fluorouracil involving 2 courses of cisplatin (70 mg/m2/day on day 1) and 5-fluorouracil (700 mg/m2/day on days 1-5). RESULTS: Complete pathological response was 17.6% in the radiochemotherapy group and 0% in the chemotherapy group respectively. No hospital mortality occurred in the radiochemotherapy group, and 1 of the 23 chemotherapy patients died in the hospital due to postoperative complications. The incidence of residual tumors was significantly higher in the chemotherapy group (34.8%) than in the radiochemotherapy group (0%). Actuarial survival in the radiochemotherapy group at 1 year was 80.2% and at 3 years 53.5%. Actuarial survival in the chemotherapy group at 1 year was 56.5% and at 3 years 30.4%. CONCLUSIONS: Histological effectiveness was greater in patients treated with preoperative radiochemotherapy than those treated with preoperative chemotherapy. The combination of radiation and low-dose fraction CDDP/5-FU thus is first choice in neoadjuvant radiochemotherapy for the advanced esophageal carcinoma.     

Metastatic urothelial cancer showing an efficacy by low-dose cisplatin

A 69-year-old man who had developed multiple distant metastases on retrocaval lymph nodes after four courses of Methotraxate, Vinblastine, Adriamycin, Cisplatin (MVAC) chemotherapy was successfully treated by intravenous infusion of low-dose cisplatin (CDDP) (10 mg/time, once per week) and oral administration of 600 mg/day 5'-deoxy-5-fluorouridine (5'-DFUR), a pro-drug of 5-FU, in an outpatient setting. A partial response (62% reduction rate) was confirmed by abdominal computed tomography (CT) scan after 7 months. Although the CDDP dosage had been reduced to 5 mg/week 1 year previously, the tumor was still reducing in size in November 2000. Combination therapy of 5'-DFUR with low-dose CDDP could become an option for advanced bladder cancer that compromises the patient's quality of life, especially when used in an outpatient setting.     

Presence of serum p53 antibodies is associated with decreased in vitro chemosensitivity in patients with esophageal cancer

Resistance to chemotherapy remains a serious problem inhibiting the successful treatment of advanced esophageal cancer. A number of studies have revealed that p53 genetic alteration and protein overexpression can predict chemosensitivity. Furthermore, p53 protein overexpression in cancer tissues has been found to induce serum p53 antibodies (p53-Abs). This study was conducted to examine whether analysis of serum p53 Abs could predict the chemosensitivity of esophageal cancer. Serum analysis of p53 antibodies was performed by enzyme-linked immunosorbent assay in 19 patients with esophageal squamous cell carcinoma preoperatively, then surgically resected specimens were stained immunohistochemically for p53 protein expression. Tumor tissues were also analyzed for chemosensitivity by the histoculture drug response assay (HDRA) using cis-dichlorodiammineplatinum(II) (CDDP), 5-fluorouracil (5-FU), and adriamycin (ADM). Serum p53-Abs were present in 47% (9/19) of the patients and immunohistochemical analysis revealed overexpression of p53 protein in 42% (8/19) of the tumors. The presence of serum p53 antibodies was significantly correlated with p53 immunoreactivity (P = 0.005). The inhibition index of patients positive for p53-Abs was significantly lower than that of patients negative for p53-Abs (P < 0.001). This tendency was also observed in the inhibition index to 5-FU. The presence of serum p53-Abs was associated with decreased in vitro chemosensitivity to CDDP and 5-FU. Thus, the detection of serum p53-Abs is suggested to be useful for predicting chemosensitivity in patients with esophageal cancer. Received: August 2, 2000 / Accepted: March 6, 2001     

Phase I Dose-Escalation Study of Docetaxel,Cisplatin, and 5-Fluorouracil Combination Chemotherapy in Patients With Advanced Esophageal Carcinoma

A dose-escalation study of docetaxel (DOC), cisplatin (CDDP), and 5-fluorouracil (5-FU; DCF combination regimen) was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD) and dose-limiting toxicities (DLT) in advanced esophageal carcinoma. Eighteen patients with esophageal carcinoma were enrolled and received DCF combination therapy at different dose levels. DLTs included febrile neutropenia and oral mucositis. DLT occurred in 2 out of 6 patients at level 2 and 3. The study proceeded to level 4, according to the protocol. The level 4 dose was defined as the MTD and the level 3 dose was defined as the RD. The RD for DCF combination chemotherapy for advanced esophageal carcinoma in the present study was 70 mg/m² DOC plus 70 mg/m² CDDP on day 1 plus 700 mg/m² 5-FU on days 1–5 at 4-week intervals. This regimen was tolerable and highly active. A phase II study has been started.Key words: Docetaxel, Cisplatin, Fluorouracil, Esophagus, Phase ILocally advanced esophageal carcinoma is often refractory to current therapeutic approaches, and its prognosis is grim.^1,2 Patients with unresectable or inoperable disease are usually treated with chemotherapy or chemoradiotherapy.^3,4 Although various chemotherapy regimens are available, esophageal cancer carries a very poor prognosis, with a survival time of less than 8.1 months with current chemotherapies used singly or in combination with 5-fluorouracil (5-FU), vindesine, mitomycin, docetaxel (DOC), paclitaxel, cisplatin (CDDP), irinotecan, vinorelbine, or capecitabine.⁵ 5-FU and CDDP combination therapy (PF) is regarded as standard,⁶ for which the median survival time is reported to be 9.2 months for responders and 5.3 months for nonresponders.⁷In recent years, a new combined chemotherapeutic regimen consisting of DOC, CDDP, and 5-FU (DCF) has received much attention for the treatment of esophageal cancer.⁸ The DCF regimen exploits the strong clinical effects of each component. However, there are few reports describing the use of a combination of DOC, CDDP, and 5-FU (DCF) for esophageal carcinoma.⁹ Therefore, we conducted a phase I clinical trial of a DCF regimen in patients with advanced esophageal carcinoma. Our aim was to determine the recommended dose (RD), maximum tolerated dose (MTD), and dose-limiting toxicity (DLT) of DCF combination chemotherapy for patients with esophageal carcinoma. Secondary objectives were to assess treatment-related toxicity and efficacy.     

Resection of hepatocellular carcinoma with tumor thrombus of the portal vein after neoadjuvant regional chemotherapy

We report a successfully managed case of far-advanced hepatocellular carcinoma (HCC) by intraarterial infusion therapy. A 55-year-old man was admitted to our hospital with abdominal pain and subileus. Abdominal ultrasonography, computed tomography, and angiography revealed HCC with obstruction of the main portal vein due to tumor thrombus. Serum levels of α-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) were elevated. Neoadjuvant chemotherapy was tried with a course of low-dose cisplatin (CDDP) +5-fluorouracil (5-FU) intrahepatic arterial infusion through the indwelling catheter via the subcutaneous reservoir port. After 7 weeks of administration (total dose CDDP 370 mg/5-FU 18.5 mg), the main tumor size was effectively reduced. Serum levels of AFP and PIVKA-II decreased markedly. Adverse effects were tolerated. Following the chemoinfusion therapy, posterior segmentectomy and thrombectomy were performed. Reconstruction of the portal vein was not necessary because we removed the tumor thrombus without resecting the portal vein. The postoperative course was uneventful, and the patient has been doing well more than 2 years after surgery, with no evidence of recurrence or metastasis. Preoperative low–dose CDDP +5-FU intrahepatic arterial infusion therapy in combination with hepatic resection may be an effective treatment for advanced HCC with portal vein tumor thrombus. Received: December 31, 2001 / Accepted: June 17, 2002 Offprint requests to: H. Kamiyama     

Treatment of renal cell carcinoma with 5-fluorouracil and alfa-interferon

Objectives

Renal cell carcinoma is relatively resistant to both chemotherapy and immunotherapy. Response, survival, duration of response, and toxicity of treatment were evaluated in patients with advanced renal cell carcinoma receiving a continuous intravenous infusion of 5-fluorouracil (5-FU) and low dose subcutaneous alfa-2b-interferon.

Methods

Between 1989 and 1994, 21 patients with advanced renal cell carcinoma underwent treatment with continuous intravenous infusion of 5-FU, 200 mg/m²/day, and subcutaneous injections of recombinant interferon alfa-2b (IFN-α), 1 x 10⁶ U/day.

Results

Objective response was observed in 9 patients (43%). Complete response occurred in 4 patients (19%): 2 with lung, 1 with bone, and 1 with liver metastasis. Partial response occurred in 5 patients (24%). Three of 4 complete responders remain alive without recurrence. Mean survival rate was 195 weeks among complete responders, 184 weeks among partial responders, and 88 weeks among nonresponders. The overall mean duration of response was 101 weeks. Responders developed progression of disease a mean of 62 weeks after the initial response to therapy. Mild dose-dependent toxicity was related to 5-FU infusion. Nearly all toxicities subsided with the temporary cessation of 5-FU infusion and/or decreasing the dose of the infusion. Few if any of the toxicities appear to be directly related to the low dose interferon injections.

Conclusions

Although this study is based on a small sample size, we believe that the encouraging complete and partial responses, apparent prolongation of survival, and manageable toxicity of this combination therapy warrant further investigation with larger randomized trials.     

Phase II study of repeated single 24-hour infusion of low-dose 5-fluorouracil for palliation in symptomatic hormone-refractory prostate cancer

BACKGROUND: To assess the efficacy and toxicity of repeated single 24-hour infusion of low-dose 5-fluorouracil for symptomatic hormone-refractory prostate cancer using relevant endpoints of palliation and biological response. PATIENTS AND METHODS: 25 patients with histologically confirmed prostatic adenocarcinoma and symptomatic progressive disease despite one or several hormonal treatments and chemotherapy were included in the study. Treatment consisted of a single 24-hour infusion of 500 mg/m(2) 5-fluorouracil (5-FU) to be repeated on day 21. This regimen was continued until either progression or serious toxicity occurred. Response was assessed by serial measurements of serum prostate-specific antigen (PSA) as well as by health-related quality-of-life instruments (EORTC QLQ-C30 and McGill-Melzack Present Pain Intensity Scale) every 3 weeks. In 10 patients with bidimensionally measurable metastases, objective responses were assessed every 3 months. RESULTS: A mean number of four courses of repeated single 24-hour infusion of 5-FU was administered (range 2-6). Toxicity was absent or mild, and no patient had to be withdrawn from therapy. All patients required analgesics prior to treatment and only 3 patients experienced a significant reduction in pain for 9 weeks, the remaining patients experienced no deterioration for a mean duration of 12 weeks (6-18 weeks). Five patients (20%) demonstrated a biological response of a 50% or greater decrease in PSA from baseline, including 2 (12%) with a 75% or greater decline for 10 weeks (range 6-16 weeks). One partial remission was observed among 10 patients with measurable lesions lasting 12 weeks; 4 patients had stable disease with a mean duration of 12 weeks. Mean survival time from the onset of treatment with 5-FU was 7 months (2-12 months). CONCLUSIONS: Though less toxic than other 5-FU regimens, repeated single low-dose 24-hour infusion is of no significant benefit in patients with symptomatic hormone-refractory prostate cancer.     

Infusional interleukin-2 and 5-fluorouracil with subcutaneous interferon-α for the treatment of patients with advanced renal cell carcinoma: a Southwest Oncology Group phase II study.

Background: A Phase II trial was conducted to determine the response rate of patients with advanced renal cell carcinoma to a three-drug combination of 5-fluorouracil (5-FU), interleukin-2 (IL-2), and interferon-alpha-2b (IFN-alpha).Methods: A 2-stage accrual plan was used that was designed to determine whether response to this regimen was consistent with a true response rate of ⩾30%. The regimen was comprised of 5 treatment days weekly for 4 weeks every 6 weeks. Each weekly treatment was comprised of 5-FU, 1750 mg/m², continuous intravenous (i.v.) infusion over 24 h followed by IL-2, 6 MIU/m²/day, continuous i.v. infusion for 4 days. IFN-alpha, 6 MU/m², was given subcutaneously on Days 1, 2, and 5.Results: Thirty-eight patients were entered on study, 3 of whom were ineligible. Among the 35 eligible patients there were 3 confirmed partial responses (PR) and 1 complete response (CR), for an overall response rate of 11% (95% confidence interval, 3–27%). One patient considered as having a PR had minimal evidence of residual disease and was free from disease progression at >2.5 years of follow-up, as was the patient with CR. Three additional patients not qualified as having a PR were showing signs of response at the time they were removed from protocol, and another patient who was removed from protocol early for management of an infection subsequently responded to the same regimen off protocol. Thirteen patients were considered nonassessable (NASS) for response, many of whom had multiple poor risk features and were unable to complete 1 cycle of treatment.Conclusions: This multicenter study failed to confirm an advantageous overall response rate for this three-drug regimen. However, there were two durable responses and indications of responsiveness not scored as PRs among patients with more favorable risk factor patterns, and many poor risk NASS patients. For these reasons, the response rate reported in the current study may be a conservative reflection of the effectiveness of this regimen.     

Adjuvant arterial infusion chemotherapy after resection of hepatocellular carcinoma with portal thrombosis: a pilot study

Background/Purpose The prognosis of hepatocellular carcinoma (HCC) with tumor thrombosis of the main trunk or major branches of the portal vein (mPVTT) is extremely poor, even if it is curatively resected. Uncontrollable multiple metastases to the residual liver are often observed within several months after the operation. We report here the results of a pilot study, showing the efficacy of adjuvant arterial infusion chemotherapy after the resection of HCC with mPVTT.Methods Twelve patients had curative resection of HCC with mPVTT. Six of the patients were treated by the arterial infusion of a chemotherapeutic agent via a subcutaneously implanted injection port after curative resection of HCC with mPVTT. The initial course consisted of the daily administration of cisplatin (CDDP) and continuous infusion of 5-fluorouracil (5-FU). This was followed by the weekly or biweekly administration of CDDP and subsequent infusion of 5-FU until the cumulative dose of 5-FU reached 15 g.Results The median overall survival time was 58.0 months with adjuvant chemotherapy and 8.0 months without adjuvant chemotherapy. The median disease-free interval was 15.0 months with adjuvant chemotherapy and 4.0 months without adjuvant chemotherapy. Adverse reactions were tolerable nausea and loss of appetite.Conclusions This chemotherapeutic regimen achieved favorable results and may be useful as adjuvant chemotherapy in treating patients after curative resection of HCC with mPVTT.     

Pharmacokinetics of excretory passage of 5-fluorouracil (i.v.) into the pancreatic juice of patients with pancreatic or biliary carcinoma: Evaluation of possible adjuvant chemotherapy

The drug, 5-fluorouracil (5-FU), is thought to be efficacious in treating human pancreatic or biliary carcinomas; therefore, to determine the optimal dosage for chemotherapeutic use in these conditions, we performed this pharmacokinetic study in which we investigate the passage of various doses of intravenously administered 5-FU into the pancreatic juice of 11 patients with pancreatic or biliary carcinoma. Whenever possible, all 11 patients, who had undergone a pancreaticoduodenectomy and had an external drainage tube, received the following three regimens: (1) a bolus injection of 5-FU, 185 mg/m² per day; (2) a continuous infusion of 5-FU, 185 mg/m² per day over 48h (CIV-I), and (3) a continuous infusion of 5-FU, 370 mg/m² per day over 48 h (CIV-II), with a sufficient wash-out period of 2 weeks between each regimen. The major findings were: (i) the percentage of the administered 5-FU dose excreted (pancreatic passage fraction; Fp) was strongly correlated with the total amount of pancreatic juice excreted over the 24-h period (Vp) of drug testing; (ii) the Fp per 100 ml Vp (Fp') was greater after the bolus treatment than after either CIV treatment; (iii) 90% of the 5-FU excreted into the pancreatic juice was present within 30min of the bolus injection; and (iv), the entire body clearance (CL_total) of 5-FU was significantly lower after the bolus injection than after either CIV treatment. It was concluded that the Fp' value was dependent on the method of 5-FU administration, that a 5-FU bolus injection probably inundates the hepatic metabolic capacity, and that the Fp' of 5-FU largely depends on the patient's ability to metabolize the drug. Therefore, the efficacy of 5-FU as an anticancer agent appears to be time-rather than dose-dependent.     

静脉结合给药的FLEP法治疗难以切除的晚期胃癌

目的:为提高胃癌新辅助化疗的效果,观察动静脉结合的FLEP化疗方法对难以切除局部晚期胃癌的疗效.方法:2003年1月至2006年1月选择30例难以切除的晚期胃癌,以FLEP法化疗.FLEP方案:5-FU 370 mg/(m2·d),持续静脉滴注20h,第1～5天;四氢叶酸钙30mg/(m2·d),静脉滴注,第1～5天;...     

Cisplatin--5-fluorouracil chemotherapy for advanced inoperable squamous carcinoma of the head and neck

Patients with locally advanced, inoperable squamous cell carcinoma of the head and neck were offered three courses of cisplatin and 96-h 5-fluorouracil (5-FU) infusion. Subsequent therapy included surgery when feasible, irradiation therapy, and a maintenance program of methotrexate (MTX)-5-FU. Thirty-three patients were evaluated prospectively. Seven patients underwent a single course of chemotherapy. Five patients underwent two courses of chemotherapy. Twenty-one patients underwent three courses of adjuvant chemotherapy. The overall response rate was 48% (16 of 33). Fifteen of 21 patients (76%) receiving three courses of chemotherapy evidenced a response; this included three complete responses (CRs) (9%). No responses were seen in patients receiving only one or two courses of chemotherapy. Among responding patients, the initial favorable response to chemotherapy was apparent after the first course of chemotherapy. Patients who failed to demonstrate any response after two courses of chemotherapy did not respond after a third course. A significant group of patients fail to respond and should be offered participation in other investigational protocols as they become available.     

Cisplatin-5-fluorouracil chemotherapy for advanced inoperable squamous carcinoma of the head and neck

Patients with locally advanced, inoperable squamous cell carcinoma of the head and neck were offered three courses of cisplatin and 96-h 5-fluorouracil (5-FU) infusion. Subsequent therapy included surgery when feasible, irradiation therapy, and a maintenance program of methotrexate (MTX)-5-FU. Thirty-three patients were evaluated prospectively. Seven patients underwent a single course of chemotherapy. Five patients underwent two courses of chemotherapy. Twenty-one patients underwent three courses of adjuvant chemotherapy. The overall response rate was 48% (16 of 33). Fifteen of 21 patients (76%) receiving three courses of chemotherapy evidenced a response; this included three complete responses (CRs) (9%). No responses were seen in patients receiving only one or two courses of chemotherapy. Among responding patients, the initial favorable response to chemotherapy was apparent after the first course of chemotherapy. Patients who failed to demonstrate any response after two courses of chemotherapy did not respond after a third course. A significant group of patients fail to respond and should be offered participation in other investigational protocols as they become available.     

A phase II study of cis-diamminedichloroplatinum and 5-fluorouracil in advanced upper aerodigestive neoplasms

Thirty patients with advanced head and neck cancer of diverse histologies received the combination of cis-diamminedichloroplatinum (CDDP) (100 mg/m²) and 5-fluorouracil (5-FU) (1,000 mg/m²/24 hours × 4 days) at 3–4-week intervals. Among all study participants, the median time to progression was 3.9 months and the median survival was 7.2 months. Among 20 patients with squamous cell carcinoma, we observed five objective regressions (25%). None of the responders had prior chemotherapy; four had extensive prior radiation therapy. Among 10 patients with non-squamous cell carcinoma neoplasms, we detected three objective responses (30%). Histopathology of the responding patients included poorly differentiated sarcoma, anaplastic carcinoma, and malignant mixed parotid tumor. Significant gastrointestinal toxicities included moderate-to-severe nausea (60%), vomiting (43%), and stomatitis (57%). Leukopenia (< 4,000 cells/mm³) and thrombocytopenia (< 130,000 cells/mm³) affected 78% and 41% of patients, respectively, without sepsis or hemorrhage.     

Results and limitations of arterial infusion therapy for liver metastases from colorectal cancer

In our institution, patients with multiple unresectable liver metastases from colorectal cancer have received 24-h continuous arterial infusion therapy of 5-fluorouracil (5-FU) 250 mg/body/day every 2 weeks for the past 11 years. Although the 5-year survival rate of those who underwent surgical resection was 35%, that of unresectable patients who received 5-FU arterial infusion was 24% at 2 years, 9% at 3 years, and 50% survived a median of 391 days. Furthermore, we were able to perform surgical resection of metastatic residual lesions in patients who responded to 5-FU arterial infusion. This therapy has proven so effective that the 3-year survival rate of these patients is now 38%, and complete cures are being achieved.     

Histologic differentiation and chemosensitivity of human head and neck squamous cell carcinomas

The chemosensitivities of 42 human head and neck squamous cell carcinomas were examined using the in vitro succinate dehydrogenase inhibition (SDI) test. The tumor tissues obtained at surgery or biopsy were exposed to five different antitumor drugs: adriamycin (ADM), cisplatin (CDDP), carboquone (CQ), 5-fluorouracil (5-FU), and 1-hexylcarbamoyl-5-fluorouracil (HCFU). The results were analyzed according to the histopathologic degree of differentiation of well, moderately, and poorly differentiated squamous cell carcinoma. The average decrease in succinate dehydrogenase activity was 43.2 +/- 24.9 for ADM, 29.0 +/- 14.2 for CDDP, 32.9 +/- 17.6 for CQ, 64.2 +/- 20.6 for 5-FU, and 26.8 +/- 16.9 for HCFU. There was a statistically significant difference in the decrease of succinate dehydrogenase activity between well and poorly differentiated squamous cell carcinomas. These data suggest that, for patients with a poorly differentiated squamous cell carcinoma, the response to anti-cancer drugs may be more satisfactory than in those with a well-differentiated squamous cell carcinoma.     

Sequential combination chemotherapy consisting of vincristine, peplomycin, methotrexate, cis-diamminedichloroplatinum (II), cytosine arabinoside and 5-fluorouracil, for advanced urothelial cancer

Two VPM-CisCF chemotherapy regimens (vincristine (VCR), peplomycin (PEP), methotrexate (MTX), cis-diamminedichloroplatinum (II) (CDDP), cytosine arabinoside (Ara-C) and 5-fluorouracil (5-FU), established using human bladder cancer xenografts in nude mice were applied for advanced urothelial cancer. VPM-CisCF (I) consisted of 0.4 mg/m2 VCR on days 1 and 4, 2 mg/m2 PEP on days 1-7, 2 mg/m2 MTX on days 2, 3, 5 and 6, 20 mg/m2 CDDP on days 8, 20 mg/m2 Ara-C on days 8 and 13, and 150 mg/m2 5-FU on days 10-12. VPM-CisCF (II) consisted of 0.6 mg/m2 VCR on days 1 and 3, 3 mg/m2 PEP on days 1-4, 3 mg/m2 MTX on days 2 and 3, 35 mg/m2 CDDP on day 4, 20 mg/m2 Ara-C on days 4 and 7, and 200 mg/m2 5-FU on days 5 and 6. These doses were adjusted for each case: the above mentioned dose x [(80/(40 + Age))2 + (Karnofsky's performance status/100)2]. VPM-CisCF (I) was administered to 6 patients (bladder cancer and transitional cell carcinoma), intra-arterially in two cases. One patient showed a complete response and survived for 7 months, three partial response (PR) surviving for 13, 8 and 37 (arterial-infused case) months, one showed minor response (MR) surviving for 4 months, and one had no change (NC) surviving for 5 months. VPM-CisCF (II) was administered to 11 patients (1 ureteral cancer, 1 renal pelvic cancer, 9 bladder cancer, and 10 transitional cell carcinoma except a case of mixed type of transitional cell carcinoma and squamous cell carcinoma). Four of the patients who had PR survived for 9, 8, 8 and 7 (alive) months, two who had MR survived for 8 and 4 months, three who had NC survived for 6, 4 and 4 months, and who two had progressive disease survived for 8 and 6 months. The major toxicities were myelosuppression and gastrointestinal symptoms, especially nausea and vomiting, but the treatment was well-tolerated.     

An experimental study of local chemotherapy for metastatic lung tumor —Isolated lung perfusion and pulmonary artery infusion—

Purpose

We evaluated the efficacy of local chemotherapy using isolated lung perfusion (ILP) and pulmonary artery infusion (PAI) in vivo to improve prognosis for patients with metastatic lung diseases.

Material and methods

Male F344 rats were used. The left lung was isolated and chemotherapeutic agents were administrated to the isolated lung by the ILP or PAI technique. Agents used were cisplatin (CDDP) and fluorouracil (5-FU), and their levels in the perfused lung and serum were measured (renal levels were also measured in CDDP groups). The results were compared with those obtained following intravenous administration (IV). In the ILP group, the left pulmonary artery and vein were clamped during perfusion. The agents were infused from the pulmonary artery, and the perfusate was collected from the pulmonary venotomy site following flushing with saline before declamping. In the PAI group, the left pulmonary artery was clamped and perfused with 0.2 ml of the agents, pulmonary arterial flow was occluded for 20 minutes, and perfusate was not collected. Rats were sacrificed 5 minutes after declamping in both groups, and the perfused lung and blood (and also kidneys in the CDDP group) were collected for pharmacokinetic examination. Histological examination of the perfused lung was also performed. Results: In the ILP group treated with 1 mg of CDDP and PAI group treated with 0.1 mg of CDDP administration, the lung CDDP levels were significantly higher and the serum and renal CDDP levels were significantly lower than those in the IV group. In the ILP group treated with 150 mg of 5-FU and PAI group treated with 10 mg of 5-FU, the lung 5-FU levels were significantly higher than those in all IV groups and the serum 5-FU levels were lower than those in the IV group treated with 10 mg and 15 mg of 5-FU. The bronchopulmonary construction was histologically maintained in the perfused lung in each group. Conclusion: We concluded that local chemotherapy using ILP or PAI could be a safe and effective choice of therapy, and this method may be clinically applicable.