A case of rectal cancer with multiple liver and peritoneal metastases that responded dramatically to low-dose 5-FU plus LV and CDDP combination chemotherapy

We have experienced successful treatment of a multiple hepatic metastasis of rectal cancer with combination chemotherapy. The patient is a 57-year-old male with bowel obstruction accompanied by rectal cancer (SE, N3, P1, H3, M (-) stage IV) who underwent a Hartmann operation with D3 lymph node dissection on July 6, 2000. The histopathological findings revealed a well-differentiated adenocarcinoma (se, INFbeta, n3, ly2, v2, p1). From the 11th postoperative day, combination chemotherapy using 5-FU 750 mg/day and LV 300 mg/day was performed once a week. When he underwent 5 combination chemotherapy treatments, adverse effects of grade 3 occurred, and the serum CEA level rose rapidly. We changed his regimen at that time. He underwent 2 courses of combination chemotherapy with 5-FU 500 mg/day and CDDP 10 mg/day for 5 days. Additional courses of combination chemotherapy with 5-FU 500 mg/day, LV 25 mg/day and CDDP 10 mg/day were performed weekly in the outpatient department. The treatment was effective, and a complete response (CR) was noted 4 months after the chemotherapy. The same combination chemotherapy was performed biweekly for one year after CR. The patient has been receiving a subsequent single administration of UFT and has remained in remission for 3 years and 7 months after surgery.     

Three successful case reports of advanced gastric cancer with chemotherapy

We report three successful cases with continuous systemic chemotherapy for advanced gastric cancer. Case 1: A 67-year-old male with gastric cancer. Abdominal CT showed the invasion in the pancreas and as a result, continuous systemic infusion of low-dose cisplatin (CDDP 20 mg/day) and 5-fluorouracil (5-FU 1,000 mg/day) was performed. This infusion chemotherapy, CDDP and 5-FU, was continued for 5 days and discontinued for 25 days. Three months after the chemotherapy, the main tumor was remarkably reduced (downstaging was obtained), and consequently, total gastrectomy was performed. Case 2: A 78-year-old male with gastric cancer and hepatic multiple metastases. Abdominal CT scan before operation did not reveal the hepatic metastasis. In the operation for distal gastrectomy, we found multiple metastases on the surface of the liver. Continuous systemic infusion of low-dose CDDP (20 mg/day) and 5-FU (1,000 mg/day) was performed. This infusion chemotherapy, CDDP and 5-FU, was continued for 5 days and discontinued for 2 days. One month after the chemotherapy, Liver metastases had almost disappeared. Case 3: A 73-year-old male had received a distal gastrectomy based on the diagnosis of gastric cancer. The tumor marker, CA19-9, immediately decreased after the operation, but had increased again. He was treated with a combination chemotherapy of TS-1 and CDDP. The treatment consisted of 4 weeks of TS-1 administration (100 mg daily) followed by a 2-week break. CDDP of 10 mg/day was infused intravenously (day 1-5). Four weeks after the infusion, CA19-9 had returned to almost normal. We conclude that the combination chemotherapy of 5-FU (or TS-1) and CDDP might be an effective treatment for advanced and metastatic gastric cancer.     

A case of unresectable advanced gall bladder cancer successfully treated by hepatic arterial chemotherapy with reservoir (HACR) using CDDP and 5-FU

A 64-year-old female was admitted for treatment of a huge tumor (10 cm in diameter) in segment S4-S5 of the liver. The lymph node (2 cm in diameter) was located posterior to the pancreas head. The patient was diagnosed with an unresectable advanced gall bladder cancer with direct invasion of the liver bed and lymph node metastasis. At first, hepatic arterial infusion of CDDP, MMC and ADM through the hepatic artery was performed. Then, hepatic arterial chemotherapy with reservoir (HACR) using CDDP and 5-FU (CDDP 20 mg/body/day, 5-FU 750 mg/body/day) was started. As a result, the primary tumor and enlarged lymph node almost disappeared in two years. Mild bone marrow suppression, nausea and vomiting were encountered, but no severe side effects were noted. We conclude that this strategy is effective for unresectable advanced cancer of the gall bladder with lymph node metastasis.     

A case of multiple liver metastases from colon cancer successfully treated with pharmacokinetic modulating chemotherapy

The present patient was a 54-year-old woman with anemia. After examination to identify the cause of anemia, she was diagnosed with sigmoid colon cancer and multiple liver metastasis. Sigmoid colectomy and insertion of an intra-hepatic arterial catheter were carried out. Histopathological examination of the resection specimen revealed well-differentiated adenocarcinoma, with a depth of tumor invasion of ss and positive lymph node metastasis. Pharmacokinetic modulating chemotherapy (PMC) was performed after the operation. The PMC consisted of oral UFT 300 to 400 mg/day every day and continuous arterial infusion of 5-FU 750 to 1,000 mg/24 h once a week. On a CT scan of the abdomen performed 6 months after the operation, the liver metastasis had disappeared and the patient was in complete remission (CR). PMC was continued, but the hepatic artery became occluded 1 year and 11 months after the operation, and so PMC was replaced by systemic chemotherapy of 5-FU plus levofolinate at 2 years after the operation. This chemotherapy was discontinued after 3 courses. At present, 2 years and 10 months after the operation, the patient remains in CR and is followed as an outpatient.     

Long-term administration of low-dose cisplatin plus 5-fluorouracil prolongs the postoperative survival of patients with esophageal cancer

To evaluate the efficacy of long-term postoperative adjuvant chemotherapy with low-dose cisplatin (CDDP) plus 5-fluorouracil (5-FU) (CDDP/5-FU), we retrospectively examined 167 patients with squamous cell carcinoma of the esophagus who received the treatment after curative surgery (R0 resection). We classified the patients into the following three groups according to their postoperative therapies and analyzed their outcomes: a) low-dose CDDP (10 mg body(-1) day(-1) x 5 days) plus 5-FU (250-500 mg body(-1) day(-1) x 5 days) repeated every 6 months for 3 years, with an oral fluoropyrimidine (5-FU 150-200 mg body(-1) day(-1) or UFT 300-400 mg body(-1) day(-1)) administered between each treatment cycle (low-dose CDDP/5-FU group, 98 patients); b) high-dose CDDP (80 mg body(-1) day(-1) x 1 day) plus 5-FU (750-1,000 mg body(-1) day(-1) x 5 days) administered once only, followed by treatment with an oral fluoropyrimidine (5-FU 150-200 mg body(-1) day(-1) or UFT 300-400 mg body(-1) day(-1)) for 3 years (high-dose CDDP/5-FU group, 17 patients); or c) surgery alone (surgery alone group, 52 patients). The 3-year survival rates were 83.7% in the low-dose CDDP/5-FU group, 61.4% in the high-dose CDDP/5-FU group, and 62.2% in the surgery alone group; the difference between the low-dose CDDP/5-FU group and surgery alone group was significant (log-rank, p<0.05). A significantly better outcome in the low-dose CDDP/5-FU group than in the surgery alone group was associated with pStage III disease (p<0.001), pN1 lymph node metastasis (p<0.001), and lymphatic invasion (p<0.01). We conclude that long-term postoperative treatment with low-dose CDDP/5-FU is therapeutically beneficial and prolongs survival in patients with esophageal cancer who have regional lymph node metastasis or lymphatic invasion.     

Neoadjuvant chemotherapy with CDDP and 5-fluorouracil for gastric cancer with serosal invasion

Many gastric cancer patients who recur peritoneally are initially diagnosed with serosal invasion. To clarify the usefulness of neoadjuvant chemotherapy with 5-fluorouracil (5-FU) +/- cisplatin (CDDP), neoadjuvant versus no preoperative chemotherapy for gastric cancer with preoperative serosal invasion was investigated. The patients were treated preoperatively with 5-FU 300 mg/m(2)/day for 2 weeks (F group; n=40), 5-FU 300 mg/m(2)/day for 2 weeks + CDDP 15 mg/m(2)/day for 2 days (FP group; n=80) or nothing (C group; n=100). A total of 78% of patients in C, 65.0% in F and 67.5% in FP group were classified as T3 or higher surgically. In patients without peritoneal metastasis, the positive peritoneal lavage cytology was 29.2% in C, 11.8% in F, and 12.2% in FP patients (p=0.0279). Serosal invasion was found histologically in 60.0% of C, 30.0% of F, and 33.8% of FP patients (p=0.001). There were no serious drug reactions and no increases in morbidity or mortality using either regimen. The 5-year survival rate was 47.0% in F and 50.9% in FP patients, but only 33.2% in C patients (p=0.0042). In conclusion, neoadjuvant chemotherapy with 5-FU +/- CDDP for gastric cancer patients with serosal invasion may reduce positive peritoneal cytology, eliminate cancer cells from the serosal surface, and improve prognosis.     

Complete response to chemoradiotherapy in a patient with synchronous double gastric and esophageal cancer

A 77-year-old man with early synchronous double primary gastric and esophageal cancer showed complete response (CR) to chemoradiotherapy (CRT) with fluorouracil (5-FU) and cis-diamminedichloroplatinum (CDDP) and 60 Gy total dose of radiation. Gastrointestinal endoscopy had revealed type IIc squamous cell carcinoma in the lower oesophagus and type IIc adenocarcinoma in the mid-stomach region. Synchronous double primary early-stage esophageal and gastric cancer was diagnosed. The patient's age and chronic obstructive pulmonary disease (COPD) contraindicated radical esophageal surgery. Therefore, we decided to first administer CRT with 5-FU and CDDP for the esophageal cancer, and subsequently perform partial gastrectomy for the gastric cancer. After the CRT, neither of the tumors recurred. CR to CRT for the esophageal cancer and CR to chemotherapy for the gastric cancer were achieved. CONCLUSION: CRT with 5-FU and CDDP can produce CR in cases of early esophageal and gastric cancer.     

A case of advanced gallbladder cancer responding to neoadjuvant intra-arterial chemotherapy

The patient was a 52-year-old female who had been diagnosed as advanced gall bladder cancer by various imaging studies. The cancer responded to neoadjuvant intra-arterial chemotherapy and was curatively resected. Since cancer had invaded the median widely, the posterior and the lateral segments of the liver according to CT imaging, neoadjuvant chemotherapy was used. The combination chemotherapy included intra-arterial chemotherapy (CDDP 10 mg + 5-FU 250 mg/day/week x5 times, EPI 10 mg + 5-FU 250 mg/day/week x3 times) through the hepatic artery and oral chemotherapy (UFT 300 mg/day for 106 days). No severe side effects were found during this chemotherapy. Imaging studies after the chemotherapy showed a partial response (PR) and curative resection (hepato-pancreato-duodenectomy with regional lymph nodes dissection) could be performed successfully. She has been disease-free without any sign of recurrence for 18 months after surgery. We conclude that this combination chemotherapy will be useful for advanced gall bladder cancer if the appropriate combinations, dosages, and administration routes are chosen.     

Effect of combination chemotherapy with nedaplatin and 5-FU for head and neck squamous cell carcinoma

Nedaplatin (254-S), which is a cisplatin (CDDP) analog, is an effective agent for head and neck squamous cell carcinoma (HNSCC). 254-S is expected to play an important role in neo-adjuvant chemotherapy (NAC) for HNSCC in place of CDDP. We have been using combination chemotherapy including CDDP, 5-FU, MTX and LV. The response rate and CR rate of this 4-drug combined chemotherapy are 87% and 33%. Thirty-six patients with HNSCC were treated with 5-FU, 800 mg/m2/day for 5 days and 254-S, 100 mg/m2 on day 4. Chemotherapy was discontinued in one patient because of allergic shock. Three patients showed a CR and 10 patients showed a PR. The response rate and CR rate of 254-S plus 5-FU chemotherapy were 37.1% and 8.6%. These were inferior to those with the 4-drug combined chemotherapy. Fourteen percent of patients showed grade 3 leukocytopenia, and 17% showed more than grade 3 thrombocytopenia. The effect of combination chemotherapy of 254-S and 5-FU was inferior to that of the previous chemotherapy including CDDP, 5-FU, MTX and LV. Further study or another combination therapy including 254-S will be essential for improving efficacy against HNSCC.     

Successful treatment of a patient with recurrent ovarian clear cell adenocarcinoma under combination chemotherapy of 5-FU (civ) and low-dose CDDP (i.v.)

Resistance to conventional chemotherapy including CDDP is the most important therapeutic problem in ovarian cancer. The combination chemotherapy of 5-FU (civ) and low-dose CDDP (i.v.) was applied to a patient with recurrent ovarian clear cell adenocarcinoma (stage IIa), which is often more resistant to systemic chemotherapy than other ovarian adenocarcinomas and is a poor prognostic factor. The patient underwent cytoreductive surgery. Then, 5-FU 375 mg/m2/day civ (days 1-5, 8-12, 15-19, 22-26) and CDDP 3.75 mg/m2/day i.v. (days 1-5, 8-12, 15-19, 22-26) were administered. After four courses of this treatment, there is no sign of recurrence. This result indicates that the combination of 5-FU and CDDP is useful in the treatment of recurrent ovarian cancers.     

A case of stage IV (A3) cervical and upper thoracic esophageal adenocarcinoma successfully treated with concurrent chemoradiotherapy

We report a case of cervical and upper thoracic esophageal adenocarcinoma with tracheal stenosis and bilateral recurrent nerve palsy. A 64-year-old man with unresectable esophageal cancer (A3, N1, M0) was treated with concurrent chemoradiotherapy. A dose of 67.4 Gy was irradiated to the cervical and upper thoracic area where the primary tumor and lymph node metastases were located, and six courses of 5-FU (250 mg/24 h/day 1-5) and CDDP (5 mg/1 h, just before radiation/day 1-5) were delivered concurrently. The esophageal tumor showed a complete response (CR), and the paratracheal lymph node metastases showed partial responses (PR). The reason these therapies were more effective against the tumor than the lymph node metastases is uncertain. The patient is no longer required to stay in the hospital, and his QOL has been improving. His condition has been maintained for 4 months, so this type of concurrent chemoradiotherapy may be recommended for cervical and upper thoracic esophageal adenocarcinoma.     

A case of gastric cancer with paraaortic lymph node metastasis responding to preoperative chemotherapy and surviving 4 years and 4 months after total gastrectomy

A 68-year-old woman was admitted to our hospital because of type 4 gastric cancer associated with paraaortic lymph node metastasis. Considered surgically incurable, she was placed on preoperative chemotherapy consisting of Methotrexate (MTX) 50 mg (day 1), CDDP 10 mg (day 2-6), 5-FU 500 mg (day 1-6) and Leucovorin (LV) 60 mg (day 2-6). Because of severe nausea and leucopenia, she could receive only 1 course of the chemotherapy. CT on January 7, 1997 (5 weeks after the chemotherapy) showed that the gastric wall thickness and the paraaortic lymph nodes swelling had decreased remarkably. She underwent total gastrectomy on January 13, 1997 (pT2, pN2, pM1 (LYM), stage IV, TNM classification). As an outpatient, she was treated with UFT-E 300 mg/day (continuous until the present) and MTX 50 mg (day 1), 5-FU 500 mg (day 1) and LV 60 mg (day 2-3) once two weeks (total 27 cycles). Four years and 4 months after surgery, although peritoneal recurrence was suspected, she has been managed at our outpatient clinic.     

Low-dose CDDP and 5-FU for head and neck cancer patients]

Combination chemotherapy with CDDP and 5-FU is one of the most effective regimens for head and neck cancer. Recent studies have focused on biochemical modulation in the combination of CDDP and 5-FU. We studied the difference in effectiveness and adverse effects between two CDDP administration schedules for CDDP-5-FU combination chemotherapy. For regimen A, CDDP was administered on 5 consecutive days from day 1 to day 5, with a daily dose of 16 mg/m2. For regimen B, CDDP was administered at 80 mg/m2 on day 1. 5-FU was administered at 600 mg/m2/day in a continuous drip infusion for 120 hours from day 1 to day 5 for regimens A and B. Twenty-seven patients with head and neck squamous cell carcinoma were included in this study, and received either regimen A or B. Thirteen patients were given regimen A and 14 regimen B. With regimen A, 3 patients showed CR and the response rate was 76.9%. With regimen B, 3 patients showed CR and the response rate was 64.3%. The rates of efficacy were not different between regimen A and B. In contrast, a difference was seen with organ toxicity. Regimen B was more toxic for renal function than regimen A, while regimen A showed greater toxicity to bone marrow function. Acute nausea and vomiting were observed more frequently with regimen B. The difference in organs and symptoms of adverse effects, according to the schedule of CDDP administration would seem to be important in the treatment of head and neck cancer patients. The schedule of CDDP administration should be adjusted depending on the renal and bone marrow functions of the patients. Because multiple infusion of CDDP proved to be efficacious, low-dose CDDP and 5-FU will have a role for patients with head and neck squamous cell carcinoma. We also introduce other reports on the efficacy of low-dose CDDP and 5-FU.     

Successful treatment of a patient with recurrent ovarian cancer by lentinan combined with intraarterial 5FU

A patient with ovarian cancer recurrent in the pelvis showed partial response to consecutive intraarterial (IA) cisplatin (CDDP) combined with continuous IA 5FU treatment and received third look operation in which the recurrent tumor could not be completely removed. The biopsied specimen revealed that the histologic type of the recurrent tumor was papillary adenocarcinoma. Postoperative IA CDDP could not produce further effect against the remaining tumor. Thereafter, the patient has been treated ambulatorily with intravenous (IV) lentinan (2mg/wk) combined with IA 5FU (without CDDP) to date. Four months after the start of this therapy, the persistent tumor which became refractory to IA CDDP disappeared completely (CR). Such a remarkable effect was accompanied by the concurrent induction of significantly enhanced IL-2 production and increased ratio of Leu3a/Leu2a possibly by lentinan. At present, performance status of the patient is 0 (normal activity) and she has been free of disease for 6 months, which is confirmed by clinical assessment including physical examination, cytologic examination, CT, scintigraphy and B scope.     

Seven patients with stage IVb advanced gastric cancer who were treated with preoperative chemotherapy

We examined the usefulness of preoperative chemotherapy using 5-FU and low-dose CDDP in patients with stage IVb gastric cancer. Between 1996 and 1998, seven patients with stage IVb gastric cancer who received preoperative chemotherapy achieved complete or partial response. One course of the chemotherapy was as follows: arterial or venous infusion of 5-FU (500 or 250 mg/day on day 1-5) and low-dose CDDP (5-10 mg/day on day 1-5) for three weeks. In addition to preoperative chemotherapy, biological response modifiers such as OK-432 and lentinan were used. We evaluated the response with abdominal or chest CT and tumor markers. Although preoperative chemotherapy did not improve the survival rate significantly, the prognosis of these patients seemed to be relatively good. Only slight side effects were found. These results suggest that preoperative chemotherapy using 5-FU and low-dose CDDP may be useful for patients with stage IVb gastric cancer.     

A case of advanced hepatocellular carcinoma with portal invasion resected after treatment by continuous intra-arterial chemotherapy with cisplatin and 5-fluorouracil

A 67-year-old male diagnosed as having inoperable advanced hepatocellular carcinoma with portal invasion was able to undergo resection after continuous intra-arterial chemotherapy with 5-fluorouracil (5-FU) and cisplatin (CDDP). These were continuously administered for 24 hours at doses of 5-FU of 250 mg and CDDP of 5 mg/day, from day 1 to day 5 in a week, repeated 6 times. In additions to the reductions of the levels of AFP and PIVKA-II from 212.6 ng/ml and 16,100 mAU/ml to 11.8 ng/ml and 12 mAU/ml, respectively, the volume of the tumor and the portal invasion were diminished remarkably. As a result, a left extended hepatectomy could be performed. No sign of recurrence was seen during 16 months of follow-up after the operation. Given the above results, continuous intra-arterial chemotherapy with 5-FU and CDDP therapy may be effective for patients with hepatocellular carcinoma.     

The prospects of the outpatient clinic or home anti-cancer chemotherapy for unresectable recurrence of colorectal cancer

In this study, we analyzed the effectiveness of anti-cancer chemotherapy at the outpatient clinic. We administered CDDP 5 mg/day every 5 days for a week with continuous systemic chemotherapy by 5-FU 500 mg/day for 3 weeks in the hospital, and in the outpatient clinic CDDP 5 mg/day every two days for a week with UFT 300 mg/day orally every day to 145 patients with unresectable recurrence of colorectal cancer. The 50% survival duration after beginning of this chemotherapy was 310.0 days. One-year and 2-year survival rates were 44.4% and 11.7%. One hundred and nine cases were evaluated. The total response rate was 19.3%, and the highest response rate was seen in metastatic lymph nodes (37.5%). The mean duration of continuation of this chemotherapy and the mean duration of staying at home was 188.2 days and 237.8 days. The mean rate of home stays was 68.6%. The group of performance status (PS) 0 or improving PS, accounted for 74.5% of all cases. The occurrence rate of adverse effects was as follows; stomatitis: 17.9%, diarrhea: 11.7% and bone marrow suppression: 13.1%. However, the occurrence rate for cases of grade 3 or 4 was only 1-4%. According to these results, this was an excellent chemotherapy to maintain the patient's QOL from the outpatient clinic.     

A successful case of lower gingival cancer with pulmonary metastases by adjuvant chemotherapy including paclitaxel, cisplatin and 5-fluorouracil following a surgical procedure

We report a successful case with pulmonary metastases from lower gingival cancer by a surgical procedure and four cycles of adjuvant chemotherapy including paclitaxel (PTX), cisplatin (CDDP) and 5-fluorouracil (5-FU). A 47-year-old woman underwent chemotherapy with CDDP and 5-FU after an operation for lower gingival squamous cell carcinoma and its neck lymph node metastases. At 4 months from the initial treatment, pulmonary metastatic lesion was resected by video-assisted thoracoscopic surgery (VATS). Fourteen months later, pulmonary metastatic lesion was found and dissected again using VATS. Furthermore, the patient was treated by adjuvant chemotherapy with PTX 135 mg/m(2) over 3 hours on day 1, CDDP 75 mg/m(2)on day 2 and 5-FU 350 mg/m(2)/day by continuous intravenous infusion on day 2 through 5. After that, there is no evidence of pulmonary recurrence for more than six years.     

Preliminary evaluation of chemotherapy with docetaxel, 5-FU, CDDP for recurrent esophageal cancer--a pilot study

A pilot study has been conducted since January 2002 to investigate whether chemotherapy with docetaxel, 5-FU, CDDP could be an effective regimen for recurrent esophageal cancer. Ten patients with recurrent esophageal cancer were treated with the combination of docetaxel 60 mg/m2 (day 1), CDDP 10 mg/body (days 1-5) and 5-FU 500 mg/body (days 1-5) at intervals of 2-3 weeks. All patients had undergone surgery, had a recurrent tumor and had already been treated with chemo-radiotherapy or chemotherapy with CDDP + 5-FU. Response evaluation in 10 patients with measurable disease: partial response 4 patients, stable disease 2 patients and progressive disease 4 patients. The main NCI-CT grade 3/4 toxicity was leukopenia (8/10). Mild to moderate nausea (> or = grade 2) occurred in 3/10 patients.     

A case of advanced gastric cancer responding to combination chemotherapy with low-dose 5-FU plus CDDP

A 56-year-old man presented with dysphagia, and was found to have a type 3 advanced gastric cancer with bilateral multiple lung metastases. This patient was treated with low-dose 5-FU plus CDDP chemotherapy. In the first course, CDDP (6 mg/m2/day) plus 5-FU (300 mg/m2/day) were infused for 5 successive days a week, but a tumor response was not achieved. Therefore, in the second course, CDDP (6 mg/m2/day) plus 5-FU (600 mg/m2/day) were infused every other day (3 days a week). In response to the treatment, both the gastric tumor and the lung metastases almost completely disappeared (reduction rate 95%), and PR was achieved. The CEA level markedly decreased, from 260.3 to 1.4 ng/ml and the patient's symptoms disappeared. Following this treatment, low-dose CDDP plus UFT therapy was performed and the PR was maintained for 12 months. This report shows a case of advanced gastric cancer that responded to low-dose 5-FU plus CDDP.