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Small cell lung cancer(SCLC)is one of the histological types of lung cancer showing the worst prognosis, and is often diagnosed as an inoperable advanced stage disease. Recently, several comprehensive genomic analyses for SCLC have shown that inactivating mutations of tumor suppressor genes such as TP53 and RB1 and MYC family gene amplifications are involved in the development and progression of SCLC. However, actionable gene alterations for targeted therapies have not yet been identified, and there has been no significant advance in the development of targeted therapies for SCLC. In a nationwide lung cancer genome screening project in Japan, LC‒SCRUM‒Japan, a large‒scale genomic analysis was prospectively performed for Japanese SCLC patients, and based on this genomic analysis, a clinical study to evaluate the efficacy of a targeted therapy for PI3K/AKT/mTOR pathway gene‒altered SCLC(EAGLE‒PAT trial)was conducted. In this article, we describe the results of the genomic analysis in LC‒SCRUM‒Japan and the EAGLE‒PAT trial, and also provide the overview of genetic alterations reported in SCLC and the current and future development of targeted therapies for SCLC.

Objective: To perform a retrospective analysis of UFT and oral leucovorin combination adjuvant chemotherapy for Stage III colon cancer patients over 76 years old, in order to evaluate both treatment efficacy and toxicity., Subjects: Between 2002 and 2011, 333 Stage III colon cancer patients had surgery performed in our institute, and we studied 25 of them on our chemotherapy regimen., Results: Patients'median age was 78 years old, with 12 men and 13 women. Of all the patients, 19 had Stage IIIa and 6 had Stage IIIb. The 3-year disease-free survival rates for Stage III and Stage IIIa patients were 65. 1% and 83. 1%, respectively, and the 3-year overall survival rate for Stage III was 79. 9%. With regard to toxicity, liver function disorder was observed in 8% of the patients, being the adverse event that occurred the most, but there was no Grade 3 or 4 toxicity., Conclusion: UFT and oral leucovorin combination adjuvant chemotherapy for Stage III colon cancer patients over 76 years showed a good response, especially for Stage III a.

Hypomagnesemia is one of the well-known side effects in patients receiving cisplatin-containing chemotherapy. However, the relevance between hypomagnesemia and cisplatin-induced nephrotoxicity remain to be completely elucidated. Although patients with esophageal and hypopharyngeal cancer are susceptible to dehydration, there is no evidence yet that magnesium supplementation for these patients will prevent nephrotoxicity during cisplatin-containing chemotherapy. The aim of this study was to examine the effect of magnesium supplementation on the prevention of cisplatin-induced nephrotoxicity for patients with esophageal and hypopharyngeal cancer. Twenty-three patients with esophageal or hypopharyngeal cancer were studied over 2 weeks. Ten of them received magnesium supplementation and 13 did not. Magnesium sulphate(20 mEq) was administered before 5-fluorouracil(800mg/m2/24 h/day 1-5)and cisplatin(80mg/m2/day 1)(FP)treatment. The maximum serum creatinine concentration of magnesium-supplemented group demonstrated a significantly lower concentration compared to the non-magnesium-supplemented group(p=0. 018). As a result, magnesium supplementation successfully reduced the incidence rate of nephrotoxicity(p=0. 038). These results showed that magnesium supplementation before FP treatment may be quite beneficial for preventing nephrotoxicity in patients with esophageal and hypopharyngeal cancer, and it is therefore recommended that magnesium be routinely supplemented during FP treatment for esophageal or hypopharyngeal cancer.

Objective: To perform a retrospective analysis of UFT and oral leucovorin plus PSK combination adjuvant chemotherapy for stage III colon cancer in order to evaluate both treatment efficacy and toxicity., Subjects: Between 2003 and 2009, 273 stage III colon cancer patients underwent surgery in our institute, and we studied 156 of them., Results: Patients' median age was 72 years old; 87 men and 69 women. Of all patients, 119 had stage IIIa and 37 had stage IIIb. The 3-year disease, free survival rates for stage III, stage IIIa and stage IIIb patients were 73. 9%and 80. 6%and 51. 4%, respectively, and the 3-year overall survival rates for stage III was 97. 6%. With regard to toxicity, liver function disorder was observed in 9. 6%of the patients as the most frequent adverse event, but there was no grade 3 or 4 toxicity., Conclusion: UFT and oral leucovorin plus PSK combination adjuvant chemotherapy for stage III colon cancer showed a good response especially for stage III a.

We retrospectively evaluated the efficacy and safety of a first-line combination chemotherapy with Docetaxel, Cisplatin, and 5-fluorouracil (DCF therapy) in nine patients with advanced esophageal cancer. Dose administrated were 75 mg/m² of Docetaxel on day 1, 75 mg/m² of CDDP on day 1, and 750 mg/m² of 5-FU on day 1-5. Complete response (CR) in two patients (22. 2%), partial response (PR)in three patients ( 33. 3%), and no change (NC) in four patients (55. 6%) were shown for main lesions, while CR in one (11. 1%), PR in five (55. 6%), and NC in three (33. 3%) were shown for lymph node metastases. Response rates of the DCF therapy were 55. 6% for main lesions and 66. 7% for lymph node metastases. Five patients who achieved PR or CR underwent esophagectomy with lymph node dissection. Toxicity from DCF therapy was grade 3 or 4 emergent adverse events (77. 8% of neutropenia, 55. 6% of febrile neutropenia, and 55. 6% of anorexia). DCF therapy improved the response rate in esophageal cancer patients, but resulted in some increase in toxicity. Prospective study with prevention of toxicity should be planned in order to evaluate first-line DCF therapy for advanced esophageal cancer.

A 65 -year-old male was admitted to our hospital because of epigastregia. Computed tomography (CT) and abdominal ultrasonography (AUS) revealed advanced gallbladder cancer and two S5 liver metastases. Selective gallbladder angiogram revealed his cystic vein was draining into the portal vein (P5), so cholecystectomy and S4a+S5-subsegmentectomy were performed. Pathological study of the resected specimens showed three liver metastases. After surgical resection lumbar metastasis was suspected, so radiotherapy and UFT at 300mg/day were started. Next, we started oral administration of S-1 alone (100mg/body) for 4 weeks followed by a 2-week rest period as one course. 100mg/day was changed to 80mg/body after 3 courses because of grade 2 neutropenia. A total of 31 courses of S-1 80mg/day were administered postoperatively for five years. The patient is alive and free of disease five years and ten months after the operation.

The combination chemotherapy with docetaxel/CDDP/5-FU(DCF)for head and neck squamous carcinoma(SCC) has been widely accepted. It seems quite natural that DCF therapy is expected to be equally effective against esophageal SCC because of their histological similarity. In this report, we present a case of unresectable advanced esophageal SCC with multiple liver metastases which showed remarkable regression by DCF therapy, with relatively slight adverse effects. The patient was a 46-year-old female, who underwent upper gastrointestinal fiber-optic endoscopy for dysphasia and was diagnosed to have upper middle thoracic esophageal SCC. Abdominal CT scan showed multiple liver metastases with para-aortic lymph node involvement. The clinical stage diagnosis was T3N4M1, Stage IVB, obviously non-resectable far-advanced esophageal SCC. Systemic chemotherapy with DCF was started as the initial treatment. The chemotherapy regimen was as follows. 5-FU 500 mg/m(2) was administered as continuous intravenous infusion through day 1 to 5, while docetaxl 60 mg/m(2) and cisplatin 50 mg/m(2) were given intravenously on day 2. Each course was followed by a 23-day drug-free period, and the entire course was repeated every 28 days. Ten cycles of this DCF chemotherapy were carried out. After 4 cycles, primary lesion was judged as complete response(CR)by endoscopy. After 8 cycles, the liver metastases were judged as CR and para-aortic lymph nodes showed a partial response(PR)by CT scan. After 10 cycles, all we could detect was a small local recurrence of the primary tumor, which was then treated with chemoradiotherapy at the outpatient clinic. Until this writing, we added 2 more cycles of DCF therapy for the recurrent para-aortic and inguinal lymph node metastasis. Three years have passed from her first visit, and the patient is still in a stable disease state. The adverse effects were grade 3 at most in both hematological and non-hematological toxicity. We conclude that DCF therapy is potentially very effective for advanced esophageal SCC.

Since pharmacokinetics in patients undergoing hemodialysis differs from that in patients with normal renal function, chemotherapy for a hemodialysis patient should be considered with due care. We administered chemotherapy of modified FOLFOX6 to a patient on hemodialysis with inoperable metastatic colorectal cancer, and measured his plasma concentration of total platinum and non-protein-bound platinum. Since there is no reported case of oxaliplatin use in patients on hemodialysis so far, we evaluated whether it could be safely used for such patients. We made a dose escalation study with 40, 50, 60, 70 and 85 mg of oxaliplatin, and evaluated the pharmacokinetics at each dose. AUC was 5.67-10.21 mg/L x h. The dialysis removal rate was 84.0%. Although this patient could accept it relatively safely without any severe side effect, the optimal dosage and the timing of hemodialysis for inoperable metastatic colorectal cancer patients should be determined by a further study using more cases.

A 74-year-old man was suffering from Borrmann type 2 advanced gastric cancer with abdominal lymph node metastases and multiple lung metastases. He started to undergo outpatient treatment with oral administration of TS-1. But pyloric stenosis was found after 6 courses of TS-1 chemotherapy, so he underwent palliative distal gastrectomy. TS-1 chemotherapy was continued afterwards, however obstructive jaundice was found. So combination chemotherapy of CPT-11 60 mg/m(2)and CDDP 30 mg/m(2)biweekly was selected as a second-line therapy after PTCD. As no side effects were found, he could be treated on an outpatient basis by CPT-11 60 mg/body and CDDP 30 mg/body biweekly. Four months has passed since the palliative operation, and the PTCD tube was successfully removed. The abdominal lymph nodes had decreased in size and the patient has maintained good QOL. Thus, combination CPT-11 and CDDP therapy could well be a new candidate for a second-line chemotherapy in outpatients.

The most conspicuous difference between Japan and Western countries in the treatment strategy for esophageal cancer is the attitude to lymph node dissection. Japanese surgeons have aimed at complete eradication of lymphatic spread of cancer cells and have reached the level of three-field lymph node dissection. In Western countries, however, surgeons rely more on chemotherapy or radiotherapy because they consider that most patients who present with esophageal cancer already have disseminated disease. Phase II studies of neoadjuvant chemotherapy and chemoradiotherapy have yielded encouraging results, and recently, positive reports on phase III studies of neoadjuvant therapy vs. surgery alone began to be announced. No such studies have included surgery with radical lymph node dissection. With the rapid advance in information technology, radical esophagectomy has gradually gained acceptance in the West, while many trials of neoadjuvant therapy have been carried out in Japan. Theoretically, the next step should be a phase III study of neoadjuvant therapy vs. surgery in which highly radical procedures such as three-field lymph node dissection are carried out.

The biochemical modulation of 5-fluorouracil (5-FU) and leucovorin (LV) has resulted in a remarkable increase of the response rate in patients with colorectal cancer. Recently, in the treatment of gastric cancer this biochemical modulation has been introduced into clinical practice and has also achieved good antitumor activity. A review of the literature indicates that 5-FU/LV therapy for gastric cancer is effective only when LV is administered at high doses (200 mg-500 mg/m2), and the efficacy of low dose LV (20 mg/m2) administration with the combination of high dose 5-FU is still unknown. Thirty-five patients with measurable recurrent gastric cancer received low dose LV and high dose 5-FU for 4 days. The schedule was as follows: iv injection of low dose leucovorin (20 mg/m2) and from one hour later 2-hour infusion of high dose 5-FU (700 mg/m2). This new treatment for recurrent gastric cancer achieved a response rate of 40.0%, and 80.0% of the patients with pronounced palliative effects measured as recurrence-related symptoms. It is very rare for 7 out of 8 patients (87.5%) to be relieved of obstructive jaundice, and we now prefer this therapy to percutaneous transhepatic biliary drainage in patients with jaundice. The toxicity of this biochemical modulation is leukopenia, stomatitis and diarrhea, and the number of patients with toxicity over grade 3 was 5 (14.3%). There was no treatment-related death.