Is there an optimal neoadjuvant therapy for locally advanced pancreatic cancer?

Treatment of locally advanced pancreatic cancer is challenging. Despite continuing research, effective treatments continue to be elusive with median survival of only 8-12 months. Treatment options for locally advanced pancreatic cancer include radiation therapy, concurrent chemoradiation or chemotherapy. It is felt that radiation therapy is a suboptimal treatment as most of patients will die of systemic disease. In the past, radiation with 5-FU was the standard treatment for locally advanced pancreatic cancer. But now radiation has been used with combination other chemo agents such as paclitaxel or gemcitabine in order to increase the efficacy. Chemotherapy such as gemcitabine alone or gemcitabine doublet also has been studied in patients with locally advanced pancreatic cancer as well with overall survival being approximately the same magnitude as chemoradiation. The exact role of chemoradiation or chemotherapy in treatment of locally advanced pancreatic cancer is yet to be defined. Hence, this review summarizes and compares of role of radiation, chemoradiation and chemotherapy in treating this disease.     

S-1 in the treatment of pancreatic cancer

S-1 is an oral 5-fluorouracil (5-FU) prodrug, which is designed to improve the antitumor activity of 5-FU by inhibiting dihydropyrimidine dehydrogenase, the key enzyme of 5-FU catabolism. Recently, two important studies on the clinical use of S-1 for pancreatic cancer have been reported from Japan. In the first study (GEST study), S-1 demonstrated non-inferiority to gemcitabine (GEM) in overall survival (OS) for metastatic or locally advanced pancreatic cancer, but combination chemotherapy with GEM and S-1 did not show superiority to GEM in OS. In the second study (JASPAC-01 study), S-1 showed superiority to adjuvant chemotherapy with GEM in OS in patients with resected pancreatic cancer. In addition to GEM, S-1 is now regarded as the key drug in the management of pancreatic cancer in Japan. To date, many studies have investigated the effectiveness of S-1 in various settings, such as first-line chemotherapy for metastatic or locally advanced pancreatic cancer, second-line chemotherapy after GEM failure, and chemoradiotherapy for locally advanced disease. In this review, we focus on recent clinical trials of S-1-based chemotherapy for advanced pancreatic cancer.     

Oxaliplatin combined with 5-FU in second line treatment of advanced pancreatic adenocarcinoma. Results of a phase II trial

BACKGROUND: The efficacy and benefit of second-line chemotherapy in advanced pancreatic adenocarcinoma has never been demonstrated although it is regularly used. PATIENTS AND METHODS: A randomized phase II study evaluating oxaliplatin alone (OXA), infusional 5-fluorouracil alone (5-FU) and an oxaliplatin/infusional 5-FU combination (OXFU) in untreated advanced pancreatic adenocarcinoma has been conducted. In this trial, a second-line treatment with the OXFU regimen (OXA 130 mg/m2 2-h intravenous (i.v.) infusion combined with 5-FU (1000 mg/m2/day, continuous i.v., days 1-4), every 3 weeks) was offered to patients progressing after single agent treatment. RESULTS: Eighteen out of 32 patients (12 males, median age 57 years) treated in the single agent arms received the OXFU combination in second-line treatment. WHO performance status was at least 2 in 61% of the patients. There was no objective response and 3 patients (17%) had a disease stabilisation. Median time to progression from the start of second-line treatment was 0.9 months. Median overall survival was 4.9 months from the start of front-line therapy and 1.3 months from the start of second-line therapy. CONCLUSION: The results of this trial bring arguments to support a modest value of second-line chemotherapy for advanced pancreatic adenocarcinoma.     

Effective treatment of locally advanced endocrine tumors of the pancreas with chemoradiotherapy

BACKGROUND/AIMS: The use of chemoradiation in the management of locally advanced pancreatic endocrine tumors has not been reported in the medical literature. Patients with unresectable tumors are often included in trials of systemic chemotherapy, and use of external beam radiation has been only described in few case reports. Given the sensitivity of pancreatic endocrine tumors to cytotoxic agents including streptozocin, doxorubicin and 5-FU, we have hypothesized that the combination of concurrent and sequential chemotherapy and radiation will yield higher response rates than acheivable with chemotherapy alone. METHODS: Six patients with locally advanced pancreatic endocrine tumors were treated with a protocol consisting of radiation concurrent with infusional 5-FU (or capecitabine) along with induction and consolidation chemotherapy (streptozocin and doxorubicin). We retrospectively determined the objective radiographic response rate. RESULTS: The objective response rate was 80%. With a median follow-up of 29 months, all six patients in the study have had continued reduction in tumor size from the time of the first posttreatment scan to the most recent scan. None of the patients have experienced local or metastatic disease progression. Treatment was well tolerated with minimal toxicity. CONCLUSION: The combination of concurrent and sequential chemoradiotherapy appears to be a highly effective treatment for locally advanced pancreatic endocrine tumors.     

Nal-IRI/5-FU/LV versus modified FOLFIRINOX and FOLFIRI as second-line chemotherapy for unresectable pancreatic cancer: A single center retrospective study

BackgroundThe preferred regimen for unresectable pancreatic cancer following gemcitabine-based chemotherapy is not well-established. This study compared the efficacy of (ⅰ) liposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU)/leucovorin (LV) (nal-IRI/5-FU/LV) versus modified FOLFIRINOX (mFFX) and (ⅱ) nal-IRI/5-FU/LV versus FOLFIRI, respectively, and the safety of the three regimens each other, as second-line chemotherapies for unresectable pancreatic cancer.MethodsThis was a retrospective single-center analysis of all patients who were administered nal-IRI/5-FU/LV, mFFX, or FOLFIRI from December 2014 to July 2021 as second-line chemotherapy for pancreatic cancer. The primary endpoint was the overall survival (OS) of all patients, excluding those with locally advanced pancreatic cancer. Regarding safety, we assessed the incidence of grade ≥3 adverse events of interest in all patients.ResultsA total of 137 patients (nal-IRI/5-FU/LV, n = 55; mFFX, n = 39; FOLFIRI, n = 43) were included. The median OS in the nal-IRI/5-FU/LV group, the mFFX group, and the FOLFIRI group was 7.4, 11.8, and 8.4 months, respectively. Compared with the nal-IRI/5-FU/LV group, the mFFX and FOLFIRI groups displayed a hazard ratio of 0.66 [95% confidence interval 0.40–1.08] and 0.87 [95% confidence interval 0.55–1.39], respectively. In the FOLFIRI group, the incidence of grade ≥3 treatment-related adverse events tended to be low among all three groups.ConclusionsGiven the trend toward longer OS in the mFFX group and the lower incidence of adverse events in the FOLFIRI group, both mFFX and FOLFIRI, as well as nal-IRI/5-FU/LV, can be treatment options for second-line chemotherapy for unresectable pancreatic cancer.     

Chemotherapy for pancreatic cancer]

Chemotherapy is expected to play an important role in the treatment of pancreatic cancer because most of pancreatic cancers are being discovered at locally advanced or metastatic stages and recurrence rate is high even after the curative resection. Gemcitabine is a key agent for the first-line therapy of advanced pancreatic cancer. It can enhance the quality of life and prolong the survival of patients. Combination of erlotinib or capecitabine with gemcitabine showed a marginal survival benefit over single-agent gemcitabine. If patient's performance state is good, gemcitabine-based platinum combination therapy showed overall survival benefit compared with gemcitabine monothrapy. If the first-line palliative chemotherapy fails, 5-FU, capcitabine, or tegafur with or without combination can be used as the second-line agents. Adjuvant chemotherapy using 5-FU or gemcitabine after curative resection has overall survival benefit. However, neoadjuvant chemotherapy has not been proven to be effective in the treatment of pancreatic cancer.     

Toxicity and efficacy of concurrent gemcitabine and radiotherapy for locally advanced pancreatic cancer.

BACKGROUND: Gemcitabine and radiotherapy are a potent combination. A clinical assessment of the therapeutic ratio for locally advanced pancreatic cancer patients has not yet been reported. AIM OF STUDY: To assess the toxicity, survival, and pattern of failure of locally advanced pancreatic cancer patients treated with concurrent gemcitabine-based chemoradiation. Patients and Methods. Between the dates of December 1996 and August 2000 51 patients with locally advanced unresectable adenocarcinoma of the pancreas were treated with concurrent gemcitabine and radiotherapy at MDACC. Patients received 250-500 mg/m2 of gemcitabine weekly x7 over 30 min and 30-33 Gy in 10-11 fractions over two weeks to the primary tumor and regional lymphatics. Severe toxicity was defined as admission > 5 d, mucosal ulceration, > 3 dose deletions of gemcitabine or toxicity resulting in surgical intervention or that resulted in death. RESULTS: The median survival was 11 mo. Overall, 37 of 51 patients had objective evidence of local progression. The actuarial rate of local progression rate at 9 mo was 70%. The 9-mo distant metastasis rate was 52%. Tumors > or = 10 cm2 had worse local control, distant control, and overall survival. Six patients underwent pancreaticoduodenectomy after therapy. After review of the imaging, only four of these patients had minimal arterial involvement, one was incorrectly staged, and one had initial inflammatory change on CT that resolved. Twelve of 51 (24%) patients suffered severe acute toxicity, and 17 of 51 (33%) patients were admitted for supportive care. CONCLUSION: Concurrent gemcitabine and radiotherapy can be a very difficult combination to administer safely. Our results do not suggest a prolongation of median survival for patients with localized pancreatic cancer treated with this therapy. It is possible that gemcitabine-based chemoradiation contributes to the margin-negative resectability of a small number of patients with minimal arterial involvement, but this benefit is obscured by the frequent toxicity encountered in most patients. Locally advanced pancreatic cancer patients should continue to be enrolled on prospective studies investigating novel combinations of cytotoxic and/or biologic agents with concurrent radiotherapy.     

Intensity modulated radiation therapy and chemotherapy for locally advanced pancreatic cancer： Results of feasibility study

AIM: To explore whether intensity modulated radiation therapy (IMRT) in combination with chemotherapy could increase radiation dose to gross tumor volume without severe acute radiation related toxicity by decreasing the dose to the surrounding normal tissue in patients with locally advanced pancreatic cancer. METHODS: Twenty-one patients with locally advanced pancreatic cancer were evaluated in this clinical trial. Patients would receive the dose of IMRT from 21Gy to 30Gy in 7 to 10 fractions within two weeks after conventional radiotherapy of 30Gy in 15 fractions over 3 weeks. The total escalation tumor dose would be 51, 54, 57, 60Gy, respectively. 5-fluororacil (5-FU) or gemcitabine was given concurrently with radiotherapy during the treatment course. RESULTS: Sixteen patients who had completed the radiotherapy plan with doses of 51Gy (3 cases), 54Gy (3 cases), 57Gy (3 cases) and 60Gy (7 cases) were included for evaluation. The median levels of CA19-9 prior to and after radiotherapy were 716 U/ml and 255 U/ml respectively (P<0.001) in 13 patients who demonstrated high levels of CA19-9 before radiotherapy. Fourteen patients who suffered from pain could reduce at least 1/3-1/2 amount of analgesic intake and 5 among these patients got complete relief of pain. Ten patients improved in Karnofsky performance status (KPS). The median follow-up period was 8 months and one-year survival rate was 35%. No patient suffered more than grade III acute toxicities induced by radiotherapy. CONCLUSION: Sixty Gy in 25 fractions over 5 weeks with late course IMRT technique combined with concurrent 5-FU chemotherapy can provide a definitely palliative benefit with tolerable acute radiation related toxicity for patients with advanced pancreatic cancer.     

Complete regression of advanced esophageal cancer with abdominal bulky lymph node metastasis treated by concurrent chemoradiotherapy using docetaxel, cisplatin, and 5-fluorouracil

In an attempt to improve survival of patients with locally advanced esophageal cancer, chemoradiotherapy consisting of cisplatin, 5-fluorouracil (5-FU), and irradiation has recently been used. For such patients, concurrent chemoradiotherapy using docetaxel in combination with cisplatin and 5-FU has been introduced and is under evaluation. We herein report an esophageal cancer patient with concomitant distant lymph node metastasis in whom a complete response was achieved by chemoradiation therapy. A 46-year-old man was diagnosed as having stage IV A esophageal cancer with synchronous bulky metastasis in the celiac lymph node, and concurrent chemoradiotherapy was started. Chemotherapy consisting of docetaxel (30 mg/m² on days 1, 8), cisplatin (60 mg/m² on day 1), and 5-FU (200 mg/m²/day, continuous infusion on days 1–14) was performed for 2 cycles. At the same time, irradiation therapy (1.8 Gy/day on 1–5 days every week for 6 weeks) was employed for both local and metastatic lesions. Although the patient experienced severe hematological toxicity throughout the course, chemoradiotherapy resulted in complete regression of both local and metastatic disease. Subsequently, he was followed as an outpatient without any maintenance therapy, and he has been free of disease for 38 months after completion of the combination therapy. Thus, concurrent chemoradiotherapy may be effective for esophageal cancer, even with visceral metastasis.     

Cancer and leukemia group B (CALGB) 89805: phase II chemoradiation trial using gemcitabine in patients with locoregional adenocarcinoma of the pancreas

Purose. Determine the safety and efficacy of twice weekly gemcitabine and concurrent radiation to the upper abdomen followed by weekly gemcitabine in patients with surgically staged, locally advanced pancreatic cancer. Methods. Patients with surgically staged, locally advanced, nonmetastatic adenocarcinoma of the pancreas were treated with intravenous gemcitabine administered twice weekly (40 mg/m²/d) for 5 wk concurrent with upper abdominal radiation (50.4 Gy in 180 cGy daily fractions over 5.5 wk). At the completion of the chemoradiation, patients without disease progression were given gemcitabine (1000 mg/m²) weekly for five cycles. Each cycle consisted of 3 wk of treatment followed by 1 wk without treatment. Disease progression and response were assessed at 6- to 8-wk intervals. Results. From February through December 1999, 43 patients were entered into this phase II trial, 39 of whom were evaluable for treatment response. The median age was 59 yr (range: 39–84 yr); there were 18 males (47%) in the study. Grade III and IV hematologic toxicity occurred in 48 and 21% of patients, respectively, and was primarily leukocytopenia and neutropenia. Grade III and IV gastrointestinal toxicities occurred in 31 and 10% of patients, respectively. There was one death attributed to sepsis. The concurrent gemcitabine and radiation portion of the study was completed without treatment interruptions in 56% of patients. The overall median survival was 8.2 mo and the median survival in the 44% of patients demonstrating a sustained CA-19-9 response was 13.5 mo. Only six patients experienced local regional progression as their first site of failure. Two patients (5%) were still alive at 35 and 41 mo posttreatment. Conclusions. These results confirm the feasibility of twice weekly gemcitabine and radiation for the treatment of pancreatic cancer. Although this treatment strategy produced good local regional control, this did not result in a survival advantage. Stratifying patients by performance status and CA-19-9 response in future trials may be of value.     

Treatment of gastric cancer

The authors focused on the current surgical treatment of resectable gastric cancer,and significance of periand post-operative chemo or chemoradiation.Gastric cancer is the 4thmost commonly diagnosed cancer and the second leading cause of cancer death worldwide.Surgery remains the only curative therapy,while perioperative and adjuvant chemotherapy,as well as chemoradiation,can improve outcome of resectable gastric cancer with extended lymph node dissection.More than half of radically resected gastric cancer patients relapse locally or with distant metastases,or receive the diagnosis of gastric cancer when tumor is disseminated;therefore,median survival rarely exceeds12 mo,and 5-years survival is less than 10%.Cisplatin and fluoropyrimidine-based chemotherapy,with addition of trastuzumab in human epidermal growth factor receptor 2 positive patients,is the widely used treatment in stageⅣpatients fit for chemotherapy.Recent evidence supports the use of second-line chemotherapy after progression in patients with good performance status     

Preoperative chemoradiation with capecitabine in locally advanced rectal cancer

BACKGROUND: Preoperative radiation therapy in combination with 5-fluoracil (5-FU) improves local tumour control in locally advanced rectal cancer. The aim of our study was to evaluate the toxicity and efficacy of preoperative chemoradiation using the oral 5-FU prodrug capecitabine in locally advanced rectal cancer. METHODS: Sixty patients with locally advanced rectal cancer were treated with preoperative chemoradiation. Radiotherapy consisted of a total dose of 50 Gy delivered in 25 fractions to the pelvis. Chemotherapy was concurrently administered and consisted of oral capecitabine only on radiotherapy days. Surgery was performed six to ten weeks after completion of chemoradiation. RESULTS: The patient population consisted of 19 females and 41 males, with a median age of 61 years. All but two patients received the full dose of chemoradiation. No grade 3 or 4 haematological toxicities developed. Two patients (3%) developed grade 3 radiation dermatitis and one a grade 3 diarrhoea. All patients underwent definitive surgery; 19 patients underwent an abdominal perineal resection (APR), 25 a low anterior resection (LAR) and 16 patients a Hartmann's procedure. One patient with a low anterior resection developed an anastomotic leakage (4%). Final pathology demonstrated eight patients (13%) with a complete pathological response. Primary tumour and nodal downstaging occurred in 67 and 84% of the patients, respectively. Two patients (3%) had an R1 resection, one after an APR and one after an LAR. CONCLUSION: Preoperative chemoradiation with oral capecitabine is safe and well tolerated in locally advanced rectal cancer patients. This preoperative treatment has a considerable downstaging effect on the tumour and lymph nodes.     

Chemotherapy for pancreatic cancer

To date, no satisfactory treatment has been developed for treatment of patients with advanced pancreatic carcinoma. The median survival of these patients is only three to six months. Of more than 30 agents evaluated over the past three decades, only 5-FU results in a response rate with 95% confidence intervals greater than 20%. Most responses are partial, of short duration, and of questionable clinical benefit. To date, efforts to improve response rates by biochemical modulation of 5-FU have been unsuccessful but additional studies are warranted and are ongoing. Although improved response rates have been reported with some drug combinations, such as streptozotocin, mitomycin and 5-FU (SMF), median survival for combination therapy is no better than that attained with single-agent therapy. Current therapeutic options for patients with advanced disease include 5-FU, supportive care, or investigational treatment in a clinical trial. In three out of four studies, patients with locally advanced pancreatic carcinoma who received combined modality therapy (radiation in combination with 5-FU) survived significantly longer than those treated with either radiation or chemotherapy alone. The brief survival advantage, however, must be considered in the context of the additional toxicity and treatment time required for the combined modality treatment. Radiotherapy in combination with 5-FU should be considered standard adjuvant therapy for patients with completely resected disease. The median survival of treated patients was 20 months and significantly longer than the surgery alone control group (11 months) (Kalser and Ellenberg, 1985; GITSG, 1987). Of greatest significance is the tail-end plateau on the survival curve suggesting that approximately 18% of patients who received combined modality therapy were cured. The results with currently available treatment for all stages of disease are poor; therefore, patients should be informed about ongoing clinical trials which may someday improve the prognosis for pancreatic cancer.     

Phase II clinical trial of 5-fluorouracil, trimetrexate, and leucovorin (NFL) in patients with advanced pancreatic cancer

Background. Advanced pancreatic cancer has limited treatment options. 5-fluorouracil (5-FU) is frequently used in the treatment of pancreatic cancer. Preclinical studies suggest synergism between trimetrexate (TMTX), 5-FU, and leucovorin (NFL). Aim. We conducted a phase II trial to evaluate the activity and safety of NFL in pancreatic cancer. Method. Eligible patients (n=21) with untreated advanced pancreatic cancer were treated with 110 mg/m² intravenous (IV) THTX on day 1 and 200 mg/m² IV leucovorin prior to 500 mg/m² IV 5-FU on day 2. Oral leucovorin (15 mg every 6 h for seven doses) started intravenous 24 h later. Results. Treatment was administered for 6 wk followed by a 2-wk rest period. Response was evaluated every 8 wk. All patients were evaluable for response and toxicity. Most patients (80%) had distant metastases. Forty-five cycles of chemotherapy were administered. The most common serious toxicities were Grade 3 diarrhea (23.8%) and nausea and vomiting (14.2%). The response rate was 4.1% (95% CI, 0–23%), median survival was 6.8 mo, and 1-yr survival was 19%. Conclusion. Treatment with NFL is well-tolerated in patients with advanced pancreatic cancer. The median survival and 1-yr survival in these patients with poor prognosis compares favorably with other treatment options.     

A phase II study of combination chemotherapy with gemcitabine, 5-fluorouracil, and cisplatin for advanced pancreatic cancer]

BACKGROUND/AIMS: Gemcitabine has been the standard regimen for advanced pancreatic cancer, but the effect on the response rate and survival is still disappointing, leading to many trials of combination chemotherapy. 5-FU and cisplatin were combined with gemcitabine in this trial, as they are synergistic with gemcitabine and each other as well. This study was aimed to assess the effectiveness and safety of combination chemotherapy with gemcitabine, 5-FU, and cisplatin for advanced pancreatic cancer. METHODS: Patients with advanced pancreatic cancer were entered into this study. Gemcitabine at a dose of 800 mg/m2 on day 1 and 8, 5-FU 1,000 mg/m2/day from day 1 to 3 for 72 hours, and cisplatin 60 mg/m2 on day 2, 24 hours after the start of gemcitabine were administered every 3 weeks. RESULTS: From December 2001 to January 2004, twenty patients were enrolled in this study. Among 17 of these patients assessable, 3 patients had a partial remission with the response rate of 23.6% (95% confidence interval, 6.2-41.0%). The median time to disease progression was 230 days and median duration of survival was 322 days. Among total of 91 cycles, leukopenia, neutropenia, and thrombocytopenia of grade 3 or 4 occurred in 12 cycles (13.2%), 12 cycles (13.2%), and 23 cycles (24.4%), respectively. Grade 3 or 4 mucositis developed at 2 cycles (2.2%), and nausea and vomiting were encountered in 3 cycles (3.3%). CONCLUSIONS: Combination chemotherapy with gemcitabine, 5-FU, and cisplatin for advanced pancreatic cancer is active and well-tolerated, warranting a phase III study.     

Three cases of locally advanced pancreatic cancer successfully treated with chemoradiation and chemotherapy

We report three cases with unresectable locally advanced pancreatic cancer (PC) treated with a combination of chemoradiotherapy (CRT) and systemic chemotherapy, using gemcitabine (GEM) and/or S-1. All three cases were diagnosed as having locally advanced unresectable PC without distant metastatic lesions based on computed tomography, endoscopic retrograde pancreatography and/or blushing cytology. In Cases 1 and 2, we applied a so-called sandwich therapy, which consisted of induction chemotherapy before CRT and maintenance chemotherapy after CRT. The induction and maintenance chemotherapy in Cases 1 and 2 used a combination of GEM and S-1, whereas maintenance therapy with GEM or S-1 was applied in Case 3. S-1-based CRT was performed in Cases 1 and 2, and GEM-based CRT in Case 3. Survivals were 27 and 65 months, respectively, in two cases, and the disease remained stable in the other case 30 months after diagnosis. We show three cases with unresectable locally advanced PC who achieved long-term survival (27–65 months) after treatment with a combination of CRT and systemic chemotherapy, using GEM and/or S-1. Our findings indicate that sandwich therapy might be particularly effective for locally advanced PC.     

Adjuvant therapy for margin positive pancreatic cancer: A propensity score matched analysis

BackgroundAdjuvant chemotherapy or chemoradiation is often recommended for resected pancreatic adenocarcinoma. We sought to examine the impact of these therapies on R1 resected pancreatic cancer.MethodsUtilizing the National Cancer Database we identified patients who underwent pancreatic resection for adenocarcinoma. Patients were stratified by resection status and adjuvant therapy.ResultsWe identified 28,440 patients who underwent pancreatic resection. Patients with tumor size >2 cm were more likely to undergo R1 resections, p < 0.001. Adjuvant therapy improved survival in all patients with median and 5-year survival: adjuvant chemotherapy (21.7 months, 17.45%), chemoradiation (23.3 months, 20.9%) vs no adjuvant therapy (19.5 months, 19.1%), p < 0.001. In the R1 resection cohort survival was also improved with adjuvant therapy with chemoradiation demonstrating the most significant improvement: adjuvant chemotherapy (15.9 months, 6.5%), chemoradiation (18.7 months, 11.2%) vs no adjuvant therapy (12.5 months, 8.7%), p < 0.001. Chemoradiation but not adjuvant chemotherapy improved survival in the R1 node negative, p < 0.004, and node positive, p < 0.001. Adjuvant chemotherapy benefited survival in R1 node positive patients, p < 0.001.ConclusionsPatients with pancreatic cancer who undergo R1 resection have significant improvement in survival when treated with adjuvant chemoradiation and adjuvant chemotherapy. However, benefits were greater in those receiving adjuvant chemoradiation.     

Phase I Trial of Gemcitabine Dose Escalation with Concurrent Radiotherapy for Patients with Locally Advanced Pancreatic Cancer

Aim: The safety and efficacy, and the dose-limiting toxicity (DLT) of the chemotherapeutic agent gemcitabine administered in conjunction with radiotherapy in patients with locally advanced pancreatic cancer are not yet established. Here, we evaluated the safety and efficacy, DLT, and maximum tolerated dose of gemcitabine with concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. Tumor response and time to progression were also assessed. Patients and Methods: Patients with previously untreated pancreatic cancer (n = 12) received gemcitabine intravenously on days 1, 8, and 15. Concurrent radiation therapy was initiated on day 1 (40 Gy in 2 Gy/day × 20 fractions, days 1–5, 8–12, 15–19, 22–26). Patients received limited-field irradiation with three-dimensional radiotherapy. Dose escalation included dose levels 1–3 (gemcitabine 400, 600, and 800 mg/m²). Results: No patient developed DLT in this study. Of the 12 patients, there were 11 sustained responses, 0 partial responses, and 1 progressive disease. Two patients with a sustained response underwent surgery after re-evaluation. The median progression-free survival was 8 months, not including the patients that underwent surgery. Conclusion: Weekly gemcitabine at a dose of 800 mg/m² with concurrent radiation therapy in patients with locally advanced pancreatic cancer was well tolerated.     

A case of complete response to esophageal cancer by a novel concurrent chemoradiation therapy.

BACKGROUND/AIMS: A combination of chemotherapy and radiotherapy (chemoradiation therapy) has recently been developed for the treatment of non-operable esophageal cancer patients. Chemoradiation therapy is based on the concept of biochemical modulation effects and radiosensitizing effects of chemotherapeutic agents. However, the optimal choice of chemotherapeutic agents and their doses, as well as chemotherapy and radiotherapy regimens have not been precisely established. METHODOLOGY: Based on our recent experience of an effective chemoradiation therapy protocol which consisted of 5-fluorouracil (5-FU) combined with daily concurrent cisplatin and radiation, in addition to the recent knowledge on the biochemical modulation between 5-FU and cisplatin or between leucovorin and 5-FU, we have developed a complete daily concurrent chemoradiation therapy for non-operated esophageal cancer as a treatment modality with curative intent. RESULTS: We report here a novel intensive concurrent chemoradiation protocol by which complete response could be achieved. A low dose of 5-FU (250 mg/body/day) was continuously infused over 24 hours followed by leucovorin (30 mg/body), and a low dose of daily cisplatin (5 mg/body) was administered 1 hour before radiotherapy (2 Gy/day). The administration schedule was 5 consecutive days, followed by a 2-day withdrawal, and then repeated weekly for 4 weeks. CONCLUSIONS: Our completely daily concurrent chemoradiation therapy is rational, effective, and safe, because an endoscopically and pathologically complete response without severe side effects was able to be achieved and this has continued for at least 6 months after chemoradiation therapy. Therefore, we believe that our completely daily concurrent chemoradiation therapy can be recommended for non-operated esophageal cancer patients.     

Intra-arterial chemotherapy of advanced pancreatic cancer: a single center experience

BACKGROUND/AIMS: The main aim of the present work was to determine response rates and time to progression in patients with locally advanced or metastatic pancreatic cancer treated with intra-arterial chemotherapy. METHODOLOGY: Nineteen chemotherapy-naive patients with measurable lesions were treated with intra-arterial 5-fluorouracil 1000 mg/m2, leucovorin 100 mg/m2, carboplatin 300 mg/m2 and epirubicin 60 mg/m2 (FLEC regimen) every 21 days. Prophylactic granulocyte colony-stimulating factors were administered on days 4-10 of each cycle. RESULTS: There were 16 patients evaluable for response, of whom 4 (25%) had a partial response, 7 (44%) showed stable disease, and 5 (31%) progressed. Marker response rate was 43%. Median time to progression was 4 months and median overall survival was 6 months. One-year overall survival was 16%. No grade 4 toxicity or severe complications relating to the angiographic procedure were observed. CONCLUSIONS: Our results show that intra-arterial FLEC is well tolerated and active against advanced pancreatic cancer.