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.     

Prospective study of definitive chemoradiotherapy with S-1 and nedaplatin in patients with stage II/III (non-T4) esophageal cancer

Background

Standard chemoradiotherapy (CRT) using 5-FU and CDDP is the optimal treatment for patients with stage II/III (non-T4) esophageal carcinoma. However, patient quality of life (QOL) cannot necessarily be maintained during this therapy, because 5-FU must be continuously infused for 24?h and CDDP administration requires a large transfusion volume. Therefore, hospitalization is unavoidable. We conducted a study of definitive CRT with S-1 and nedaplatin.

Methods

The study was conducted between July 2004 and December 2006. Eligibility criteria were stage II/III (non-T4), PS 0?C2, age 20?C79?years, and adequate organ function. S-1 80?mg/m² was given on days 1?C14, and nedaplatin 90?mg/m² on day 1 every 4?weeks. Patients received two courses with concurrent radiotherapy of more than 50?Gy.

Results

Twenty patients (age range, 50?C75?years; PS 0/1, 8/12; stage IIA/IIB/III, 11/2/7) were enrolled. Grade 4 leukopenia, thrombocytopenia, and anemia occurred in 15%, 10%, and 5% of patients, respectively. Grade 3 nonhematotoxicity included esophagitis in 3 patients (15%) and anorexia in 2 (10%). One patient developed febrile neutropenia; another developed an esophageal fistula. Complete response was achieved in 80%. The 3-year overall survival rate was 58.0%. Thirteen subjects received treatment as outpatients.

Conclusions

S-1 and nedaplatin in combination with radiotherapy is feasible, and toxicity is tolerable. This treatment method has the potential to shorten hospitalization and maintain patient QOL without impairing the efficacy of CRT.     

Neoadjuvant chemoradiotherapy followed by esophagectomy versus definitive chemoradiotherapy in resectable stage II/III (T1-3N0, 1M0) esophageal squamous cell carcinoma

Background There are two intensive modalities for the treatment of resectable esophageal carcinoma: esophagectomy and definitive chemoradiotherapy (CRT). Esophagectomy with preoperative CRT was retrospectively compared with CRT alone in resectable stage II/III esophageal squamous cell carcinoma. Methods Seventy-four patients with resectable stage II/III (T1-3N0, 1M0) esophageal squamous cell carcinoma were treated with preoperative CRT by 5-fluorouracil (5-FU) 700 mg/m² on days 1 to 5, nedaplatin 80 mg/m² on day 1, and concurrent radiation for a total of 30 Gy in 3 weeks. If patients decided to undergo surgery, esophagectomy from the thoracoabdominal approach was carried out 6 weeks after the completion of CRT (CRT + Surg group, n = 51). If patients decided not to undergo surgery, they were treated with one more course of CRT (CRT-alone group, n = 23). Results There was no significant difference in overall survival between the two groups (P = 0.1006), whereas the disease-free survival in the CRT + Surg group was improved compared with the CRT-alone group (P = 0.0186). In the patients with clinical stage III carcinoma or with regional lymph node metastasis, the overall survival rate was significantly improved in the CRT + Surg group compared with the CRT-alone group. The rate of local failures in the CRT + Surg group was significantly lower compared with the CRT-alone group (P = 0.0011). Conclusions Preoperative CRT followed by esophagectomy provides better local control, but does not prolong overall survival, compared with definitive CRT. However, in clinical stage III or N1, esophagectomy with preoperative CRT could contribute to the improvement of survival in esophageal squamous cell carcinoma.     

Late toxicity in complete response cases after definitive chemoradiotherapy for esophageal squamous cell carcinoma

Background We retrospectively investigated long-term toxicity after concurrent chemoradiotherapy (CRT) for patients with esophageal squamous cell carcinoma (ESCC). Methods Concurrent chemoradiotherapy was performed in 110 patients with T1 to T4 disease containing M1 lymph node (LYM) disease. Chemotherapy consisted of protracted infusion of 5-fluorouracil 400 mg/m² per 24 h on days 1 to 5 and 8 to 12, combined with 2-h infusion of cisplatin 40 mg/m² on days 1 and 8. Radiation treatment of the mediastinum at a dose of 30 Gy in 15 fractions was administered concomitantly with chemotherapy. A course schedule with a 3-week treatment and a 2-week break was applied twice, with a total radiation dose of 60 Gy. For the assessment of toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring schema was adopted. Results A total of 81 patients were recruited in patients with stage I to IVA. Of 34 patients with complete response, 1 patient died as a result of acute myocardial infarction. Grade 2, 3, and 4 late toxicities occurred with the following incidences: pericarditis in 3 patients, 1 patient, and 2 patients, respectively; heart failure in 0, 0, and 3 patients; pleural effusion in 2, 3, and 0 patients; and radiation pneumonitis in 0, 0, and 1 patient, respectively. Conclusions Definitive chemoradiotherapy for ESCC is effective with substantial toxicities. Further investigation is warranted to minimize the normal tissue toxicities.     

A phase I dose escalation study of S-1 with concurrent radiotherapy in elderly patients with esophageal cancer

Background

Concurrent chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) and cisplatin (CDDP) are often associated with significant incidence of toxic effects in elderly patients with esophageal cancer. This phase I trial was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of S-1, an oral 5-FU derivative, when given with radiotherapy in elderly patients.

Methods

Patients who were age of 70 years or older with histologically confirmed esophageal cancer, and had an Eastern Cooperative Oncology Group (ECOG) score of 0–2 were eligible for this study. Radiotherapy was administered in 1.8 Gy fractions 5 times weekly to a total dose of 54 Gy. S-1 was administered on days 1–14 and 29–42 at the following dosages: 60, 70, and 80 mg/m²/day. Trial registration: {"type":"clinical-trial","attrs":{"text":"NCT01175447","term_id":"NCT01175447"}}NCT01175447 (ClinicalTrials.gov).

Results

Twelve previously untreated patients were enrolled in this study. No grade 3 or 4 toxicity was observed in six patients treated at the 60 and 70 mg/m² dose levels. DLT was observed in four of six patients treated at the 80 mg/m² dose level. Two patients developed grade 3 esophagitis, one patient developed grade 3 esophagitis and pneumonitis, and one patient developed grade 3 thrombocytopaenia. Endoscopic complete response (CR) was observed in eight patients (66.7%). The median progression free survival (PFS) was 20 months and median overall survival was 29 months.

Conclusions

The MTD of S-1 was 80 mg/m², and the recommended dose (RD) for phase II studies was 70 mg/m². This regimen was well tolerated and active in elderly patients with esophageal cancer, meriting further investigation in phase II studies.     

Metastatic basaloid-squamous cell carcinoma of the esophagus treated by 5-fluorouracil and cisplatin

Basaloid squamous cell carcinoma （BSC） of the esophagus is a rare malignant disease. We report here a patient with recurrent esophageal BSC, who was successfully treated by systemic chemotherapy containing 5-fluorouracil （5-FU） and cisplatin （CDDP）. A 57-year-old woman was diagnosed as having SCluamous cell carcinoma of the esophagus upon endoscopic examination. Curative esophagectomy with lymph node dissection was performed under the thoracoscope. The pathological diagnosis of the surgical specimen was BSC. Five months after operation, the patient was diagnosed as having a recurrence of the BSC with metastases to the liver and spleen, and a right paraclavicular lymph node. She was given systemic chemotherapy consisting of continuous infusion of 800 mg/d of 5-FU and 3 h infusion of 20 mg/d of CDDP for 5 consecutive days every 4 wk. The metastatic lesions in the spleen and right paraclavicular lymph node disappeared, and the liver metastasis was apparently reduced in size after 2 courses of chemotherapy. The tumor regression was seen over 6 courses, with progression afterwards. Although subsequent treatment with CPT-11 and CDDP was not effective, docetaxel and vinorelbine temporarily controlled the tumor growth for 2 mo. 5-FU and CDDP combination may be useful for the patients with advanced BSC.     

A case of small-cell esophageal cancer with chronic renal failure undergoing hemodialysis safely treated with cisplatin and etoposide

A 54-year-old male undergoing hemodialysis was admitted to our hospital because of difficulty in swallowing. Esophagography and esophageal endoscopy revealed an irregular ulcerated lesion in the cervical esophagus. It was diagnosed as a small-cell esophageal cancer from the biopsy sample. Computed tomography showed a tumor infiltrating the trachea and a few lymph node metastases in the cervix, upper mediastinum, and abdomen. The patient was started on chemotherapy with cisplatin (CDDP) and etoposide (VP-16), which had been reported to be effective for small-cell lung cancer. The patient was treated with CDDP (80 mg/m²) on day 1 and VP-16 (100 mg/m²) on days 1, 3, and 5, every 4 weeks. On the days of chemotherapy, hemodialysis was started as soon as possible after completion of administration of the agents. No severe side effects were observed. After 4 courses of therapy, the patient achieved a partial response.     

Results of a retrospective analysis of gemcitabine as a second-line treatment after chemoradiotherapy and maintenance chemotherapy using 5-fluorouracil in patients with locally advanced pancreatic cancer

Background  Many studies of concurrent chemoradiation therapy with 5-fluorouracil (5-FU) for locally advanced pancreatic cancer have been reported with a median survival time of approximately 10 months. Recently, gemcitabine (GEM) has been administered immediately after chemoradiation. The clinical outcome of chemoradiation therapy in conjunction with 5-FU and second-line chemotherapy with GEM after disease progression has not been clarified. Methods  Patients with locally advanced pancreatic cancer were treated with concurrent radiation therapy (1.8 Gy/fraction; total dose, 50.4 Gy) with 5-FU (200 mg/m² every day) until disease progression, followed by GEM (1000 mg/m², days 1, 8, 15, and every 4 weeks) as second-line therapy. Results  Of the 18 patients with locally advanced pancreatic cancer who received chemoradiation therapy with 5-FU, there were three partial responses, giving a response rate of 17%. The median time to progression was 170 days. The median survival time was 443 days. During chemoradiation therapy, the incidences of grade 3 or 4 anorexia, nausea, mucositis, and gastric ulcer were 33%, 22%, 17%, and 17%, respectively. Sixteen patients received second-line chemotherapy with GEM, of whom one patient had a partial response. The median time to progression from the initiation of GEM was 113 days, and median overall survival time was 231 days. Major toxicities were hematological toxicities: grade 3 or 4 leukopenia in 75% and anemia in 31%. Conclusions  The treatment strategy with concurrent chemoradiation and maintenance chemotherapy with 5-FU followed by second-line chemotherapy with GEM may be an option for locally advanced pancreatic cancer.     

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.     

Nedaplatin concurrent with three-dimensional conformal radiotherapy for treatment of locally advanced esophageal carcinoma

AIM:To evaluate the efficacy and toxicity of nedaplatin(NDP)concurrent with radiotherapy in the treatment of locally advanced esophageal carcinoma.METHODS:Sixty-eight patients with locally advanced esophageal carcinoma were randomized into either a NDP group(n=34)or a cisplatin(DDP)group(n=34).The NDP group received NDP 80-100 mg/m2iv on day 1+leucovorin(CF)100 mg/m2iv on days 1-5+5-fluorouracil(5-FU)500 mg/m2iv on days 1-5.The DDP group received DDP 30 mg/m2iv on days 1-3+CF 100 mg/m2on days 1-5+5-FU 500 mg/m2iv on days 1-5.The treatment was repeated every 4 wk in both groups.Concurrent radiotherapy[60-66 Gy/(30-33f)/(6-7 wk)]was given during chemotherapy.RESULTS:There was no significant difference in the short-term response rate between the NDP group and DDP group(90.9%vs 81.3%,P=0.528).Although the 1-and 2-year survival rates were higher in the NDP group than in the DDP group(75.8%vs 68.8%,57.6%vs 50.0%),the difference in the overall survival rate was not statistically significant between the two groups(P=0.540).The incidences of nausea,vomiting and nephrotoxicity were significantly lower in the NDP group than in the DDP group(17.6%vs 50.0%,P=0.031;11.8%vs 47.1%,P=0.016;8.8%vs 38.2%,P=0.039).There was no significant difference in the incidence of myelosuppression,radiation-induced esophagitis or radiation-induced pneumonia between the two groups.CONCLUSION:NDP-based concurrent chemoradiotherapy is effective and well-tolerated in patients with locally advanced esophageal carcinoma.NDP-based regimen has comparable efficacy to DDP-based regimen but is associated with lower incidences of gastrointestinal and renal toxicity.     

Successful treatment of pulmonary metastases associated with advanced hepatocellular carcinoma by systemic 5-fluorouracil combined with interferon-α in a hemodialysis patient

A 54-year-old man maintained on hemodialysis had a relapse of multiple pulmonary metastases after multimodal therapy for primary hepatocellular carcinoma (HCC). He was treated with tegafur-uracil (UFT; 400 mg/day) and interferon alfa (IFN-α; 5 × 10⁶ units three times per week) for 4 weeks. Following this he was treated with systemic 5-fluorouracil (5-FU; 1000 mg/day, 5 days per week) and cisplatin (CDDP; 10 mg/day, 5 days per week for 2 weeks). The response to the above treatments was inadequate; pulmonary metastasis deteriorated. Finally, we selected systemic chemotherapy of 5-FU (750 mg/day, 5 days per week) and recombinant IFN-α-2b (3 × 10⁶ units three times per week) for 2 weeks. This therapy resulted in excellent shrinkage of pulmonary metastases, without severe adverse reactions. Hemodialysis was performed three times a week. We report a case of successful treatment of pulmonary metastases by systemic combination chemotherapy of 5-FU–IFN, previously unsuccessfully treated with UFT–IFN and 5-FU–CDDP in a patient on hemodialysis. Further studies are needed to select appropriate drugs with fluoropyrimidine-based systemic chemotherapy, and to analyze the pharmacokinetics of those agents in hemodialysis patients with HCC and extrahepatic metastases.     

Feasibility of postoperative adjuvant chemotherapy of cisplatin plus vinorelbine for completely resected non-small-cell lung cancer: A retrospective study in Japan

BackgroundThe efficacy of postoperative adjuvant cisplatin (CDDP)-based chemotherapy, such as the combination of CDDP and vinorelbine (VNR), has been established for surgically resected non-small-cell lung cancer (NSCLC). However, the optimal treatment schedule and dosage for CDDP and VNR are unknown. We evaluated patient compliance with and the safety of adjuvant chemotherapy of CDDP at 80 mg/m² administered on day 1 plus VNR at 25 mg/m² administered on days 1 and 8, every 3 weeks.MethodsMedical records of 100 surgically resected NSCLC patients, treated with a combination of CDDP and VNR at the Shizuoka Cancer Center between February 2006 and October 2011, were retrospectively reviewed.ResultsEighty-three (83%) patients completed the planned 4 cycles of CDDP plus VNR and 59 (59%) received the planned doses. Sixty-eight percent of the patients experienced a decreased neutrophil count (grade 3/4 toxicity); 1%, a decreased platelet count; and 4%, febrile neutropenia. No treatment-related deaths were noted in this study. Univariate analysis of the factors influencing patient compliance with this adjuvant chemotherapy showed that neither patient characteristics nor surgical procedure was significantly associated.ConclusionsOur results indicated that adjuvant chemotherapy with CDDP at 80 mg/m² administered on day 1 plus VNR at 25 mg/m² administered on days 1 and 8, every 3 weeks, was feasible for surgically resected NSCLC cases.     

Small-cell carcinoma manifesting systemic lymphadenopathy combined with adenocarcinoma in the gallbladder: aggressiveness and sensitivity to chemotherapy

Small-cell carcinoma of the gallbladder is a very rare tumor. In this report, we describe a patient with small-cell carcinoma combined with adenocarcinoma in the gallbladder. The patient was a 70-year-old man, who clinically manifested systemic lymphadenopathy. An incisional biopsy of Virchow's lymph node revealed small-cell carcinoma. Abdominal computed tomography (CT) showed massive multiple paraaortic lymph node swelling and a round mass in the gallbladder, although chest CT did not show any abnormal masses in the lung. After two courses of chemotherapy (PVP therapy; cisplatin [CDDP], 80mg/m², day 1, intravenous injection; and etoposide [VP-16], 50mg/m², every day, per oral intake; given every 3 weeks) were performed, the systemic lymphadenopathy had completely diminished and only the gallbladder tumor remained on clinical examinations. Endoscopic retrograde cholangiopancreatography (ERCP) revealed nodular tumors in the gallbladder fundus. Cholecystectomy with partial resection of the liver was performed. Pathological examination revealed small-cell carcinoma combined with adenocarcinoma of the gallbladder. We discuss the characteristics and the treatment of this rare tumor.     

Induction chemotherapy followed by chemoradiotherapy for T4M0 esophageal cancer

Purpose

In Japan, chemoradiotherapy (CRT) is primarily indicated for T4 esophageal cancer for curative intent or when aiming for downstaging. However, CRT yields a low rate of complete response, is associated with a high incidence of complications such as fistula, and often results in the emergence of severe lymph node metastasis or distant organ metastasis after the therapy. A safer and more effective treatment strategy is needed. The aim of this study is to evaluate the efficacy of the combination of induction chemotherapy and subsequent CRT for T4M0 esophageal squamous cell carcinoma.

Patients and methods

In our institute, 97 consecutive patients with T4M0 esophageal cancer underwent CRT between 2000 and 2007. Of these, 47 patients who received induction chemotherapy before CRT were eligible for the present retrospective analysis. The regimen of induction chemotherapy was FAP therapy (fluorouracil 700?mg/m²/day, cisplatin 14?mg/m²/day on days 1?C5, doxorubicin 30?mg/m²/day on day 1) administered every 4?weeks. After one to five courses of FAP therapy, concurrent CRT at a dose of 60?C66?Gy in 30?C33 fractions was undergone.

Results

Induction chemotherapy, which preceded CRT, was effective in 21 patients (47%; responder) and ineffective in the remaining 26 patients (47%; non-responder). Better survival was achieved in the responder than in the non-responder group: the mean survival time (MST) and 1-year survival rate were 14.3?months and 66.7%, respectively, in the former, and 9.1?months and 33.6%, respectively, in the latter group. Treatment-related death occurred in 3 (6%) of the 47 patients receiving induction chemotherapy because of the progression of the radiation pneumonitis.

Conclusion

Induction chemotherapy followed by CRT is expected to improve the survival rate without increasing severe therapy-associated complications in patients with T4M0 esophageal cancer.     

A patient with esophageal squamous cell carcinoma who had a complete pathological response to neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil

We report a case of a 51-year-old man with esophageal cancer who had a complete pathological response to preoperative chemotherapy with a combination of docetaxel, cisplatin and 5-fluorouracil (DCF). Endoscopy and esophagography showed a type II tumor 8 cm in diameter, located in the upper thoracic esophagus. On computed tomography the diagnosis was T3N1M0, stage III disease according to TNM classification. Before surgery, the patient received DCF therapy, consisting of docetaxel (60 mg/m²) on day 1, cisplatin (60 mg/m²) on day 1, and 5-fluorouracil (800 mg/m²) on days 1–5. The patient had grade 3 hematological toxicity, but two courses were administered as scheduled. After chemotherapy, esophagography and computed tomography showed that the tumor had shrunk. Esophagectomy with three-field lymph node dissection was performed. Histopathologically, an ulcer scar was found, with no residual cancer cells. There were no metastases in dissected lymph nodes. This regimen is considered to have a high potential.     

Phase I study of concurrent selective lymph node late course accelerated hyper‐fractionated radiotherapy and pemetrexed,cisplatin for locally advanced esophageal squamous cell carcinoma

The optimized concurrent chemoradiotherapy has not been established for patients with advanced esophageal squamous cell carcinoma (SCC). The aim of the present study was to evaluate the safety and efficacy of concurrent chemotherapy and selective lymph node (SLN) late course accelerated hyperfractionated (LCAF) intensity modulated radiotherapy (IMRT) for the patients with thoracic SCC. Twelve patients with T3‐4N0‐1M0‐1a thoracic esophageal SCC were included. The total dose of SLN LCAF IMRT was 59.6 Gy/34 fractions in 5.4 weeks. The concurrent chemotherapy protocol was as following: cisplatin 10 mg/m² on days 1–5 and 22–26, pemetrexed in escalating doses, from the base level of 500 mg/m² once every 21 days. The primary objectives were to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose limiting toxicities (DLTs). Secondary end point included determination of preliminary radiographic response rates. As a result, three patients were enrolled in dose level 1 with pemetrexed 500 mg/m² and nine patients in dose level 0 with 400 mg/m², respectively. At dose level 1, DLTs occurred in two of three patients. However, only two of nine patients in Level 0 developed DLTs. The complete response and partial response were observed in eight and four patients, respectively. Furthermore, no patient experienced cancer progression with a median follow‐up of 9 months. In conclusion, the concurrent SLN LCAF IMRT and chemotherapy is feasible. The MTD of pemetrexed in this regimen was 500 mg/m² and RD was 400 mg/m². Although toxicities were common, the protocol was safe, well tolerated, and achieved an encouraging outcome.     

A observational study of the efficacy and safety of capecitabine versus bolus infusional 5-fluorouracil in pre-operative chemoradiotherapy for locally advanced rectal cancer

Background and objectives

This study is to evaluate the safety and efficacy of preoperative radiotherapy (RT) combined with bolus infusional 5-fluorouracil (5-FU) or oral capecitabine in patients with locally advanced rectal cancer (LARC).

Materials and methods

Seventy-four patients were retrospectively analyzed. Twenty-seven patients were treated with 5-FU (350?mg/m² IV bolus) and leucovorin (20?mg/m² IV bolus) for 5?days/week during week 1 and 5 of RT. Forty-seven patients were treated with capecitabine (850?mg/m², twice daily for 5?days/week). Both groups received the same RT course (45–50.4?Gy/25 fractions, 5?days/week, for 5?weeks). Patients underwent surgery in 6?weeks after completion of the chemoradiotherapy. Data of the observational study were collected.

Results

Grade 3 or 4 toxicities occurred in 40.7% (5-FU) and 19.1% (capecitabine) of the patients (P?=?0.044). Six patients in the 5-FU group (22.2%) and six patients in the capecitabine group (14%) achieved complete response. Primary tumor (T) downstaging were achieved in 51.9% (5-FU) and 69.8% (capecitabine) of the patients. The pathological ypT0-2 stage was 40.7% (5-FU) and 67.4% (capecitabine) (P?=?0.028).

Conclusions

In consideration of the better ypT0-2 downstaging rate, less severe toxicities, and no need for indwelling intravenous device on oral capecitabine regimen, the administration of oral capecitabine with RT may be a more favorable option in the neoadjuvant treatment for LARC.     

High-dose chronomodulated infusion of 5-fluorouracil (5-FU) and folinic acid (FA) (FF<Subscript>5–16</Subscript>) in advanced colorectal cancer patients

Purpose . The best way to deliver infusional 5-fluorouracil (5-FU) and folinic acid (FA) has yet to be determined. The aim of this prospective phase II trial was to verify the tolerability, activity and efficacy of chronomodulated 5-FU-FA (FF_5–16) every 3 weeks in 48 untreated patients (group A), and 28 pretreated and four non-measurable, advanced colorectal cancer (ACC) patients (group B).Methods The sinusoidal delivery of both drugs started at 10.00 p.m. and ended at 10.00 a.m., with peak flow at 4.00 a.m. for 5 consecutive days. The initial 5-FU dose was 900 mg/m²/day with intra-patient dose increase at 1,000 and 1,100 mg/m²/day, at the second and third course, respectively; FA was injected at a fixed dose of 150 mg/m²/day (Garufi et al.1997).Results Neither death from toxicity nor hematological toxicities were encountered. Maximal toxicity consisted of Grade 3 oral mucositis in 41% of patients, in only 8% of 535 courses. It was possible to achieve objective responses in 31% of untreated patients, with a progression free survival (PFS) of 7 months, median survival of 14 months and a 2-year survival rate of 28%. Similar results for PFS and survival were obtained in pretreated patients as well. Univariate analysis and multivariate analysis showed that response was related to the occurrence of mucositis and diarrhea (p=0.03 and p=0.0007) and to performance status (PS) (p=0.01). Quality of life, measured with the EORTC QLQ-C30+3 questionnaire, was unaffected by treatment and was better in patients with good PS and responsiveness.Conclusions In this chronomodulated FF_5–16 phase II study, the probability of obtaining a relevant tumor reduction was significantly correlated with a patient variable such as PS, and toxicity variables such as mucositis and diarrhea. This observation and the validation of predictive factors for QoL deserve further investigation in ACC patients.     

Epirubicin,cisplatin, and protracted infusion of 5-FU (ECF) in advanced intrahepatic cholangiocarcinoma

Purpose Intrahepatic cholangiocarcinoma usually presents late in the clinical course and has a poor prognosis. No effective systemic therapy is currently available. This study aimed to determine the efficacy and toxicity of the ECF regimen (epirubicin, cisplatin. and 24-h continuous infusion of 5-FU) in advanced intrahepatic cholangiocarcinoma.Patients and method On day 1, epirubicin 50 mg/m² and cisplatin 60 mg/m² were administered i.v., repeated every 21 days. 5-FU (200 mg/m²/day was given continuous i.v. via an ambulatory infusion pump throughout the treatment course. A total of 24 patients (15 men and nine women) with advanced intrahepatic cholangiocarcinoma between August 1996 and April 2002 were enrolled in this study.Results Of the 20 evaluable patients, two had partial response (10%) and nine had stable disease (45%), including two minor response. Grade 3/4 neutropenia was observed in six patients, while grade 3/4 thrombocytopenia was seen in five patients. There was no neutropenic infection or thrombocytopenic bleeding during any of the cycles of chemotherapy.Conclusion ECF regimen is well-tolerated but is not an effective treatment for advanced intrahepatic cholangiocarcinoma. Newer clinical trials with combination drugs should be developed.     

Phase I and II trials of subcutaneously administered rIL-2, interferon alfa-2a, and fluorouracil in patients with metastatic renal carcinoma

Purpose: A phase I followed by a phase II trial utilizing rIL-2, IFNα, and 5-FU were conducted in patients with unresectable and/or metastatic renal cell carcinoma. Methods: Treatment consisted of: rIL-2 at 5.0 × 10⁶ IU/m² SQ on days 1–5 for 4 weeks, rHuIFNα-2a at 5.0 × 10⁶ U/m² SQ on days 1, 3, and 5 for 4 weeks, and 5-FU by IV bolus on days 1–5 during week 1. In the phase I study, patients were treated at varying doses of 5-FU: I-none, II-250 mg/m², III-300, and IV 375. A phase II trial was then conducted utilizing the same schedule and maximum tolerated dose (MTD) for 5-FU. Results: Twenty patients were entered into the phase I trial. Dose-limiting toxicity included grade III nausea and vomiting, and one sudden cardiac death. The MTD for 5-FU was determined to be 300 mg/m². In the phase II trial, a median of two cycles of therapy was administered to 25 evaluable patients. Toxicity was moderate and consisted primarily of fevers, chills, fatigue, nausea/vomiting, and anorexia. Grade IV thrombocytopenia, consistent with ITP, developed in one patient each on the phase I and phase II trial. Seven partial responses were seen among 25 patients treated in the phase II trial for a 28% (CI 12–49%) response rate. Conclusions: The addition of 5-FU to rIL-2 and rHuIFNα-2a appears to increase the toxicity of this therapy. Randomized trials will be required to determine if efficacy is enhanced. Received: 1 May 2000 / Accepted: 21 September 2000