Metastatic Esophageal Carcinoma Research Articles

A prospective phase I/II trial of capecitabine with escalating mitomycin C and oxaliplatin in patients with advanced or metastatic esophageal carcinoma

15555 Background: In preclinical studies, mitomycin C (MMC) was found to upregulate thymidine phophorylase thereby enhancing cytotoxic activity of capecitabine. Moreover, capecitabine shows promising activity in combination with oxaliplatin in patients with esophageal cancer. Therefore, we conducted a prospective phase I/II trial of the combination of capecitabine, MMC, and oxaliplatin in patients with unresectable advanced esophageal carcinoma. Methods: Capecitabine (2,000 mg/m2, bid, d1–14) and oxaliplatin (100 mg/m2, q3 weeks) were kept constant while MMC was escalated: 6–10 mg/m2, q 6 weeks. Results: 25 pts (3 F, 22 M) received 171 cycles (median 7). Median age was 64 years (41–70). Dose-limiting toxicities were grade 4 thrombocytopenia or grade 4 neutropenia. No patients died from adverse events related drug toxicity. The maximal tolerable dose (MTD) for MMC was 6 mg/m2, q6 weeks. Partial response was seen in 10/25 pts (40%), stable disease in 11/25 pts (44%) and progressive disease in 4/25 pts (16%). Median progression-free survival was 8.9 months (95% CI, 6.2–11.6), and median overall survival was 13.3 months (95% CI, 10.8–15.8). Conclusion: The triple regimen of capecitabine, MMC and oxaliplatin is well tolerated and shows substantial clinical activity in unresectable esophageal carcinoma. The high survival rates suggest the need for prospective randomized studies of this treatment strategy. Updated results will be presented. No significant financial relationships to disclose.

Cullen's sign associated with metastatic esophageal carcinoma

Cullen's sign refers to the presence of periumbilical ecchymosis and is most often recognized as a manifestation of hemorrhagic pancreatitis. However, lesser-appreciated etiologies include ruptured ectopic pregnancy, leaking aortic aneurysm, and intraabdominal malignancy. We report the case of a patient with metastatic adenocarcinoma of the esophagus who developed Cullen's sign shortly before death. Based on this case and previously reported cases, malignancy-associated Cullen's sign portends a dismal prognosis, and may be considered a pre-terminal finding.

Concurrent Chemoradiotherapy or Endoscopic Stenting for Advanced Squamous Cell Carcinoma of Esophagus: A Case-Control Study

We evaluated the role of chemoradiotherapy (CRT) for patients with inoperable squamous esophageal cancer. Patients with locally advanced or metastatic squamous esophageal carcinoma who received CRT were recruited. The CRT consists of continuous infusion of 5-fluorouracil at 200 mg/m(2)/day, and cisplatin at 60 mg/m(2) on days 1 and 22, with concurrent radiotherapy for a total of 50 to 60 Gy in 25 to 30 fractions over 6 weeks. Efficacy was assessed by endoscopy and computed tomographic scan before and 8 weeks after completion of the treatment program. Median survival and the need for palliative esophageal stenting were compared with another group of patients who received endoscopic stenting. From 1996 to 2003, a total of 36 consecutive patients (33 male, mean +/- SD age 63.2 +/- 9.5 years) with T4 disease (81%) with or without cervical nodal metastasis (50%) received CRT, while 36 patients treated with endoscopic stenting alone were recruited as controls. Both groups were comparable in demographics, pretreatment dysphagia score, comorbidities, and tumor characteristics. CRT was completed in 32 patients (89%). There was no treatment-related mortality. Tumor volume was greatly reduced after CRT in 19 patients. Four patients (11%) received salvage esophagectomy 9 to 42 months after CRT. Compared with the stenting group, CRT statistically significantly improved 5-year survival (15% vs. 0%, P = .01), median survival (10.8 months vs. 4.0 months, P < .005), and need for stenting (22% vs. 100%, P = .005). Palliative CRT can effectively improve the symptoms of dysphagia in patients with inoperable squamous esophageal carcinoma. It results in better survival compared with endoscopic stenting in these patients.

Acute Epidural Hematoma Secondary to Skull Metastasis from Esophageal Carcinoma

The skull may be a site of metastasis in malignancies such as carcinoma of the breast, prostate, lung, and multiple myeloma. The majority of patients with skull metastases are asymptomatic or present with localized swelling which is often painless. While subdural hematoma has been commonly associated with metastatic disease involving the dura, hemorrhage from a skull metastasis remains a rare occurrence. We present the case of acute epidural hematoma resulting from metastatic esophageal carcinoma to the skull.

A phase II study of capecitabine and cisplatin (XP) as first-line chemotherapy in patients with advanced esophageal squamous cell carcinoma

The combination of 5-fluorouracil (5-FU) and cisplatin (FP) remains the mostly used regimen for metastatic esophageal squamous carcinoma. This phase II study assessed the efficacy and safety of capecitabine/cisplatin (XP) as a first-line chemotherapy in a homogenous cohort of patients with metastatic or recurrent esophageal squamous cell carcinoma. Patients received 60 mg/m(2) of cisplatin intravenously (IV) on day 1 and capecitabine 1,250 mg/m(2)/dose orally twice a day on days 1-14. Treatment cycles were repeated every 3 weeks until the documented disease progression, unacceptable toxicity, or patient's refusal. Immunohistochemical studies against thymidylate synthase (TS) and thymidine phosphorylase (TP) were performed to seek predictive markers for treatment response. Between December 2003 and March 2006, 45 patients entered the study. All patients had histologically proven squamous cell carcinoma of the esophagus. The overall response rate (ORR) was 57.8% (95% CI, 43.3-72.2) with 0 CR and 26 PRs. The median duration of response in responders was 4.6 months (1.0-15.6 months). With a median follow-up duration of 25.7 months (10.8-42.6 months), the median time to progression was 4.7 months (95% CI, 2.5-7.0) and the median survival time was 11.2 months (95% CI, 8.5-13.9). Common grade 3 or 4 non-hematological adverse events were anorexia (18/191, 9.4%), fatigue (9/191, 4.7%), constipation (6/191, 3.1%), hand-foot syndrome (6/191, 3.1%) and diarrhea (4/191, 2.1%). The most common grade 3 or 4 hematological adverse events were neutropenia (33/191, 17.3%), followed by leucopenia (11/191, 5.8%), anemia (2/191, 1.0%) and thrombocytopenia (1/191, 0.5%). There was no treatment-related death. Neither TS nor TP showed predictive value for treatment response. The XP regimen demonstrated a promising antitumor activity in metastatic esophageal squamous cell carcinoma, which may potentially replace the FP regimen.

Phase II studies on docetaxel alone every third week, or weekly in combination with gemcitabine in patients with primary locally advanced, metastatic, or recurrent esophageal cancer

The purpose of these studies was to compare efficacy and toxicity of docetaxel alone with the combination of gemcitabine and docetaxel for treatment of metastatic esophageal carcinoma. These studies enrolled patients with histopathologically verified squamous cell carcinoma or adenocarcinoma of the esophagus or cardia. Between March 1997 and June 1999, 52 patients were enrolled in the initial Phase II study (Study 1). They were scheduled for treatment with docetaxel 100 mg/m2 every third week as a 1-h infusion. The second Phase II study between September 2000 and March 2003 included 65 patients (Study II). They were given docetaxel 30 mg/m2, administered as a 30-min i.v. infusion weekly for four times, followed by 2 weeks of rest, and gemcitabine starting with a dose of 750 mg/m2 (if well-tolerated 1,000 mg/m2) on days 1 and 15, followed by 3 weeks of rest. A new cycle began on day 36. Patients were premedicated with betamethasone 8 mg p.o. on the evening before, and 8 mg i.v. 30-60 min before the docetaxel infusion. Response was confirmed by computed tomography and assessed at 12 and 24 weeks. Toxicity was assessed according to WHO scales. In study I, 38 out of the 52 enrolled patients were valuable. Two patients experienced complete remission (CR) (5%), 10 patients partial remission (PR) (26%), nine patients stable disease (SD) (24%), and 17 patients showed progressive disease (PD) (45%). Toxicity mainly involved leukopenia, which in some cases required hospitalization and treatment with antibiotics. In Study II, 46 out of the 65 enrolled patients (70%) were assessable. Out of these, three patients (7%) had CR, eight patients (17%) had PR, 10 patients (22%) had SD, and 25 (54%) PD. Overall response was 24% while an additional 22% showed stable disease. Toxicity mainly consisted of leucopenia and pain. Docetaxel as a single agent is active in esophageal cancer, both in treatment naive and in previously treated patients with recurrent disease. The overall response rate was 31%, with a good-safety profile. The addition of gemcitabine is well tolerated, but adds no efficacy. Weekly administration of docetaxel may be less effective. It demonstrates moderate efficacy and the doses used provide an acceptable safety profile.

Rare cerebellar metastases from oesophageal carcinoma

Metastatic oesophageal carcinoma to the brain is an uncommon diagnosis that may cause abnormal neurological findings. The case of a 56-year-old man who presented with brain secondaries as an initial manifestation of carcinoma of oesophagus is presented and the unique characteristics highlighted. Patient survival was for 12 months after initial presentation and treatment. Oesophageal carcinoma is a recognised cause of intracerebral metastatic tumours, though this is an uncommon occurrence.

Metastatic esophageal carcinoma masquerading as inflammatory breast carcinoma

A 50-year-old Caucasian woman with a history of esophageal adenocarcinoma presented with a 3-week history of right breast swelling and progressive erythema. Twenty-two months prior to presentation, she had been diagnosed with adenocarcinoma of the esophagus (T3,N1,M1a) and underwent neoadjuvant chemoradiotherapy followed by surgical resection. On physical examination, the right breast was red, swollen (40% larger than the contralateral breast), tender to palpation, and warm to the touch (Fig. 1). No mass was palpable. On the basis of the clinical findings, inflammatory breast carcinoma was suspected. A punch biopsy revealed a poorly differentiated adenocarcinoma with extensive involvement of dermal lymphatics (Fig. 2). The clinical and histologic differential diagnosis included inflammatory breast carcinoma vs. metastatic esophageal adenocarcinoma to the skin of the breast. To resolve this question, immunohistochemical stains for estrogen and progesterone receptors and CDX-2 (BioGenex, San Ramon, CA, USA) were performed. CDX-2 is an intestinal homeobox gene expressed in gastrointestinal epithelium and gastrointestinal tumors. The tumor nuclei were positive for CDX-2 but negative for both steroid receptors (Fig. 3), confirming the diagnosis of metastatic esophageal adenocarcinoma.

Phase II Trial of Gemcitabine Plus Irinotecan In Patients With Esophageal Cancer

Metastatic esophageal carcinoma is an incurable disease with median survival duration of 6 to 8 months. Based on preclinical data suggesting a dose-dependent synergy between gemcitabine and irinotecan we have conducted a phase II trial in patients with advanced or metastatic esophageal carcinoma. Patient eligibility included a diagnosis of squamous cell or adenocarcinoma of the esophagus/gastroesophageal (GE) junction, metastatic or recurrent disease, no CNS metastasis, no prior chemotherapy, prior adjuvant/neoadjuvant chemotherapy was allowed, no prior gemcitabine or irinotecan, performance status of 0 to 2 and adequate organ function. Patients received gemcitabine 1000 mg/m2 and irinotecan 100 mg/m2 given day 1 and day 8, every 3 weeks. The primary end point was the 6-month survival rate. The secondary end point was to assess qualitative and quantitative toxicities. Fifty-seven eligible patients were accrued. There were 4 treatment-related deaths. The primary grade 3 to 4 toxic events were diarrhea, dehydration, neutropenia, thrombocytopenia, anemia, and anorexia; and 4 episodes of grade 3 to 5 febrile neutropenia, 1 fatal. The study was designed to detect a difference between the null hypothesis of 30% 6-month survival and the alternative hypothesis of 50% 6-month survival. The Kaplan-Meier estimate of 6-month survival is 56% (95% CI: 43-69%), with a median of 6.3 months. The median time to progression was 3.7 months. The 6-month progression-free survival estimate is 25% (95% CI: 13-36%). The length of survival suggests that this combination has benefit similar to platinum containing regimens, however, the toxicity is substantial and is unlikely to prove superior to platinum containing regimens.

Successful treatment for esophageal carcinoma with lung metastasis by induction chemotherapy followed by salvage esophagectomy: Report of a case

We here report a case of a 51-year-old man with lung metastasis from esophageal carcinoma that was initially treated by combination chemotherapy consisting of fluorouracil and nedaplatin. Because metastatic disease disappeared, salvage esophagectomy was performed. Although chest wall recurrence developed at the thoracotomy wound, prolonged survival of 48 mo was achieved by local tumor resection and additional chemotherapy. This combination chemotherapy is regarded as a promising and considerable treatment for metastatic esophageal carcinoma.

Value of baseline positron emission tomography for predicting overall survival in patient with nonmetastatic esophageal or gastroesophageal junction carcinoma

The value of baseline positron emission tomography (PET) for predicting overall survival (OS) or disease-free survival (DFS) is unclear in patients with nondistant metastatic (locoregional only) esophageal carcinoma. The authors tested the hypothesis that, in this setting, the number of PET abnormalities (NPA) would correlate with OS and DFS. The authors of the current study analyzed patients with localized esophageal carcinoma (Stages II and III) who had a baseline PET and endoscopic ultrasonography (EUS) and were all treated with chemoradiotherapy followed by surgery. The standardized uptake value (SUV) of PET avid lesions were evaluated for: SUV of the primary, NPA, peak SUV, and total SUV. Correlations were performed with baseline EUS results, OS, DFS, and clinical and pathologic response. Forty-seven patients who underwent chemoradiotherapy followed by surgery were analyzed. Most patients had clinical Stage III cancer. NPA was significantly associated with OS (Cox model, P = 0.02; log-rank test, P = 0.04) and DFS (P = 0.04). Patients with NPA > 1 had a death hazard ratio of 4.49 (reference, NPA = 1). In a multivariate analysis, NPA was independently predictive of OS (P = 0.03). Alternatively, SUV of the primary tumor, peak SUV, total SUV, and EUS clinical stage did not correlate with the type of response, OS or DFS. Data from the current study suggest that for nondistant metastatic esophageal carcinoma, baseline PET can predict patient outcome. Baseline NPA (> 1), reflecting the regional nodal metastases, is an independent predictor of OS. Baseline PET may become a useful stratification factor in randomized trials and for individualizing therapy.

Phase II study of capecitabine and cisplatin as first-line therapy in patients with recurrent or metastatic esophageal carcinoma

4221 Background: 5-Fluorouracil and cisplatin remains as the standard treatment for metastatic esophageal carcinoma, producing response rates of 20 - 35% in phase II trials. Preclinical studies suggest synergistic anti-tumor activity of capecitabine (X) and cisplatin (P). XP has demonstrated activity in advanced gastrointestinal cancer (Kim et al, Ann Oncol 2002;13:1893). Methods: This non-randomised open label phase II study evaluated the efficacy and safety of capecitabine 1250 mg/m2 on days 1 to 14 twice daily and cisplatin 60 mg/m2 on day 1 every 21 days as first-line chemotherapy in metastatic or recurrent esophageal cell carcinoma patients. Patients with; histologically proven, bidimensionally measurable, metastatic esophageal squamous cell or adenocarcinoma, age 18 - 75 years, with a performance status 0 - 2, no prior chemotherapy, life expectancy > 3 months, signed written informed consent were eligible. Results: From May 2003 to Nov 2004, 20 patients were prospectively enrolled. The median age was 60 years (47 - 71) and male:female ratio was 19:1. In total, 76 cycles were administered with a median of 4 cycles per patient (range, 1 - 9 cycles), and 17/20 patients were evaluable for response (3 inevaluable pts included; 1 patient with broncho-esophageal fistula after 1st cycle; 1 patient’s refusal for further chemotherapy; too early for assessment in 1 patient). The objective RR was 47.1% (95% CI, 23.4 - 70.8) with no CR and 8 PRs. Six patients (35.3%) had SD and only 3 patients (17.6%) had PD. Median OS of all patients was 11.1 months (95% CI, 9.3 - 13.0 months). Median TTP was 5.8 months (95% CI, 4.0 - 7.6 months). In total of 76 cycles administered, grade 3/4 hematological toxicities were observed as follows: neutropenia (13.2% of all cycles), anemia (1.3%). Grade 3/4 non-hematological toxicities included anorexia (13.2%), constipation (5.3%), and diarrhea (4.0%). Grade II/III hand-foot syndrome occurred in 15% and 10% of patients, respectively. Conclusions: XP chemotherapy showed a very promising preliminary anti-tumor activity and was well tolerated with convenient administration as a first-line treatment for patients with metastatic esophageal carcinoma. Supported by Roche Korea. No significant financial relationships to disclose.

Phase II study of paclitaxel and cisplatin for metastatic or recurrent esophageal cancer

4076 Background: Paclitaxel, an agent with broad antitumor activity, is one of the most active agents against esophageal cancer. Reduced tolerance to toxic chemotherapy is main problem in patients with metastatic or recurrent esophageal cancer resulted from larger tumor burden, older ages, and comorbidities. In this study, we performed a phase II study to assess the activity of the paclitaxel and cisplatin in metastatic or recurrent esophageal cancer. Methods and Patients: From April 1999 and June 2003, 32 patients with metastatic or unresectable esophageal cancer recurring after previous treatments were enrolled into this study. All patients had ECOG PS 0–2, adequate bone marrow and renal function, total bilirubin < 2mg/dl. Patients received biweekly paclitaxel (90 mg/m2 in a 3-h infusion) followed by cisplatin (50 mg/m2), and were re-evaluated after every three cycles of chemotherapy. Results: 32 patients have been enrolled with the following characteristics: median age 60 years, M/F 32/0, PS 0/1/2: 9/18/5. A total of 151 cycle gave been given (median 5.1 cycles/patient). Grade 3–4 toxicity included: neutropenia: 4 patients (13%), thrombocytopenia/anemia: 1 patients, respectively (3%), asthenia: 7 patients (22%), nausea/vomiting: 3 patients (9%), neuropathy: 0. One patient (3%) responded completely, and 12 patients (38%) showed a partial response; in 9 patients (28%) the disease remained stable, and in 10 patients (31%) it progressed. The objective response rate was 41%; greater responses were seen in the chemotherapy- or radiotherapy-naïve patients than in the other patients (P=0.049) The median duration of response was 4.8 months, and the median overall survival in all patients was 7 months (95% CI, 5.13–8.87). The 1-year and 2-year survival rates were 28.1% and 7.1%, respectively. Conclusion: Biweekly combination chemotherapy with paclitaxel and cisplatin seems to be an active regimen in metastatic or recurrent esophageal carcinoma with acceptable toxicities. No significant financial relationships to disclose.

Haematuria as a presentation of metastatic oesophageal carcinoma

Haematuria is a classical symptom of urological disease often signifying a primary bladder cancer. Rarely, however, the presence of blood in the urine can be due to secondary spread of tumours into the bladder from distant sites. Notably this has been reported to occur in breast cancer, malignant melanoma and gastric cancers. Haematuria due to spread from a primary oesophageal cancer to the bladder has never been reported. We present a case of haematuria confirmed histologically to be due to metastases from a primary oesophageal tumour. Oesophageal cancer is capable of spread to all three neighbouring compartments (abdomen, chest and neck) and therefore has the potential to spread to unusual sites. Clinicians should always carefully regard haematuria in a patient previously treated for cancer and retain a high index of suspicion for distant metastases as being the cause.

Principles and techniques of biopsy with special reference to fine-needle aspiration cytology

Fine-needle aspiration (FNA) cytology is an inexpensive, effective and (generally) safe procedure for diagnostic sampling of superficial masses. In the UK, it has attained central importance in the management of palpable lesions of the breast and thyroid gland. The use of image guidance means that aspiration of impalpable and deep-seated lesions is routine in radiological practice in the UK. The aim of the FNA procedure is to collect sufficient representative material from the lesion to enable a cytological diagnosis ‘i.e. based on the appearance of dispersed individual cells and cell groups’ to be made. As well as its role in the primary diagnosis of tumours, FNA cytology in very useful in the staging of malignant tumours. For example, endoscopic ultrasound-guided FNA of a paraoesophageal lymph node can detect metastatic oesophageal carcinoma. Another useful role for FNA is in diagnosing recurrence of malignancy, particularly lymphoma. Clinical FNA procedures are described and potential causes of an inadequate ‘i.e. non-diagnostic’ aspirate are discussed. Various modalities of image guidance are discussed and methods of slide preparation compared. The role of special techniques such as immunocytochemistry and fluorescence in situ hybridization is illustrated by means of diagnostic scenarios. The uses and limitations of FNA cytology of the breast, thyroid, lymph nodes and salivary glands are discussed.

Metastatic Esophageal Carcinoma Masquerading as Inflammatory Breast Carcinoma

Metastasis to the breast from extramammary neoplasms is rare. Such metastatic neoplasms can mimic inflammatory breast carcinoma clinically and histologically, presenting a diagnostic challenge. A 50‐year‐old woman with a history of esophageal adenocarcinoma in clinical remission presented with rapid onset unilateral breast swelling with warmth and erythema. Based upon the clinical presentation, an underlying breast carcinoma was suspected. A punch biopsy revealed a poorly differentiated adenocarcinoma with extensive involvement of the dermal lymphatics. The clinical and histologic differential diagnosis included inflammatory carcinoma secondary to a primary breast carcinoma vs. metastatic esophageal adenocarcinoma to the skin of the breast. To resolve this question, immunohistochemical stains for estrogen and progesterone receptors and CDX‐2 were performed. CDX‐2 is an intestinal homeobox gene that is expressed in intestinal epithelium and tumors with intestinal differentiation including esophageal adenocarcinoma. CDX‐2 expression has not been reported in breast carcinoma. The tumor cells were positive for CDX‐2 but negative for both steroid receptors. The diagnosis of metastatic esophageal adenocarcinoma to the skin of the breast was confirmed. This case emphasizes the importance of confirming the tumor lineage in inflammatory carcinoma of the breast. CDX‐2 can be a useful tool in establishing a gastrointestinal origin of cutaneous metastases.

A phase II trial of gemcitabine (gem) &amp; cisplatin (cis) in advanced esophageal cancer (AEC)

4034 Background: Current cisplatin based regimens for the treatment of AEC are disappointing with response rates between 25 and 45% and median survival of around 9 months. Gemcitabine (Gem) is active against a range of tumour types. Preclinical models suggest synergistic cytotoxic activity for Gem and Cisplatin (Cis), and in phase II trials this combination is active in NSCLC, head & neck cancer and bladder cancer. Methods: This non-randomised open label phase II study evaluated the efficacy and safety of Gem 1250 mg/m2 on days 1, 8, and Cis 75 mg/m2 on day 1 every 21 days in AEC. Patients with; histologically proven, bidimensionally measurable, locally advanced or metastatic oesophageal carcinoma (squamous or adenocarcinoma), aged >18yrs, with a performance status 0–2 and life expectancy >3 months, and able to give informed consent were eligible. Interim review after 19 patients were enrolled suggested that this was unacceptably toxic, subsequent patients were treated with Gem 1000mg/m2 and Cis 75mg/m2. ...

NY-ESO-1 expression and its serum immunoreactivity in esophageal cancer.

NY-ESO-1, a member of the cancer/testis antigen (CTA) family, elicits humoral and cellular immune responses in patients with advanced cancer. Unresectable or metastatic esophageal carcinoma patients do not benefit from the present multimodality treatment regimens in terms of survival. The objectives of this study were to analyze the antibody response to NY-ESO-1 antigen in patients with esophageal cancer and to determine the potential of NY-ESO-1 for use in tumor-specific immunotherapy. Serum from 69 patients with esophageal cancer was investigated for antibody production against NY-ESO-1 by Western blot analysis. Also analyzed by immunohistochemistry were 56 tissue samples from these patients for NY-ESO-1 protein expression. NY-ESO-1 protein expression was found in 18 of 56 (32%) esophageal carcinomas. Serum immunoreactivity specific for NY-ESO-1 was found in 9 patients (13%) of whom 8 were in the advanced stage (stages III and IV). There was no relationship between clinicopathologic features and serum immunoreactivity for NY-ESO-1. NY-ESO-1 protein expression was detected in three of five antibody-positive patients whose tissue was available for analysis. Survival analysis showed no significant difference between antibody-positive and antibody-negative patient groups. A humoral immune response to NY-ESO-1 antigen was established in patients with advanced esophageal cancer. NY-ESO-1 is a good candidate for vaccine-based immunotherapy for advanced esophageal carcinoma.

Vinorelbine and cisplatin in metastatic squamous cell carcinoma of the oesophagus: response, toxicity, quality of life and survival

BackgroundVinorelbine and cisplatin are active against squamous cell oesophageal carcinoma. The purpose of this phase II study was to evaluate the efficacy and safety of vinorelbine plus cisplatin in previously untreated patients with metastatic squamous cell oesophageal carcinoma and to estimate the progression-free survival, overall survival and quality of life (QoL) of the patient population. Patients and methodsSeventy-one eligible patients were entered into a study of vinorelbine 25 mg/m2 on days 1 and 8 plus cisplatin 80 mg/m2 on day 1, every 3 weeks. Degree of dysphagia relief was monitored and QoL was measured using the EORTC QLQ-C30. ResultsAll eligible patients were assessed for response and 24 achieved a confirmed partial response (33.8%; 95% confidence interval 23–46); the median duration of response was 6.8 months, progression-free survival was 3.6 months and median survival of the whole group was 6.8 months. Toxicity was mainly related to neutropenia (grade 3/4 in 41% of patients). At cycle 2, 43% of the patients reported at least a moderate improvement in global health status/QoL and 25% experienced a large improvement. ConclusionsVinorelbine plus cisplatin represents a well-tolerated active palliative regimen for patients with advanced squamous cell carcinoma of the oesophagus. This combination may offer a better therapeutic index than cisplatin–5-fluorouracil.

Optimisation of 5-fluorouracil (5-FU)/cisplatin combination chemotherapy with a new schedule of hydroxyurea, leucovorin, 5-FU and cisplatin (HLFP regimen) for metastatic oesophageal cancer

To improve the efficacy and tolerance of the 5-fluorouracil (5-FU)/cisplatin combination in metastatic esophageal cancer, we designed a new therapeutic schedule, the HLFP regimen. 42 patients with metastatic oesophageal adenocarcinoma (n=10) or squamous cell carcinoma (n=32) were prospectively enrolled in the study. All had bidimensionally measurable disease. The HLFP regimen consisted of twice-monthly oral administration of hydroxyurea 1 g/m2 on days 0, 1 and 2; a 2-h infusion of leucovorin 200 mg/m2 and a bolus of 5-FU 400 mg/m2 followed by a 22-h infusion of 5-FU 600 mg/m2 on days 1 and 2; and, every two cycles, 80 mg/m2 cisplatin on day 3. Relief of dysphagia and other symptoms were monitored, together with body weight changes. Major objective responses were observed in 24 patients (57%, 95% Confidence Interval (CI): 42–72%), including four complete responses (10%). The median progression-free survival and overall survival times were 8 and 12.7 months, respectively. Weight gain was observed in 48% of patients, and dysphagia improved in 76%. Grade 3-4 toxicity occurred in 40% of patients, with grade 4 neutropenia in 12% and grade 3 thrombocytopenia, vomiting and diarrhoea in 7–9% of patients. There were no treatment-related deaths. These results suggest that the HLFP regimen is an active and well-tolerated chemotherapy for metastatic oesophageal carcinoma.