Carcinoma, Squamous Cell, Adenocarcinoma of the Esophagus and Gastric Cardia
Conditions
Keywords
Histologically confirmed squamos cell carcinoma or adenocarcinoma of the esophagus and gastric cardia.Suitable for surgery.
Brief summary
The purpose of this randomized study is to clarify if neoadjuvant radiochemotherapy gives a higher degree of complete histological response than neoadjuvant chemotherapy before surgery in patients undergoing treatment for cancer of the esophagus or cardia.
Interventions
DRUGChemotherapy
Cisplantin 100 mg/m2 day 1. 5-fluoracil 750 mg/m2/24 hours infusion day 1-5. Three cycles. In the chemoradiation arm the radiotherapy start week 4 and continuing until week 7. Dose adjustet according to current LPK and TPK values.
RADIATIONRadiochemotherapy
Cisplantin 100 mg/m2 day 1. 5-fluoracil 750 mg/m2/24 hours infusion day 1-5. Three cycles. In the chemoradiation arm the radiotherapy start week 4 and continuing until week 7. Dose adjustet according to current LPK and TPK values.
Sponsors
University Hospital, Umeå
Region Örebro County
Sahlgrenska University Hospital
Ullevaal University Hospital
Haukeland University Hospital
Oslo University Hospital
St. Olavs Hospital
Malarhospital Eskilstuna
Karolinska University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Histologically verified squamos cell carcinoma, adenocarcinoma of the esopohagus or gastric cardia (type II) * Tumor located in cervical oesophagus, not requiring laryngo-esophagectomy. Patients with performance status 0-1 axxording to WHO scale and with resectable tumours, as assessed at the prerandomisation evaluation * Adequate haemotological function, defined as having WBC \> 3 x 10(9)/litre and platelets \> 100 x 10 (9)/litre. * Adequate renal function defined as having normal serum creatinine level and/or calculated glomerular filtration rate \> 60 ml/min. * Tumour stage: T1Ni, T2N0, T2N1, T3N0, T3N1, M1a
Exclusion criteria
* Pregnancy and/or lactation. Women of childbearing ages can be included and provided that adequate contraceptive methods are used * Patients with diabetes complications (e.g. rethinopathy, neuropathy) as well as patients with uncontrolled cardiac disease or myocard infarction within 12 months are considered unsuitable for chemoradiotherapy. * Concomitant malignancy (\< 5 years since diagnosis) that can interfere the interpretation of study results, ongoing antitumoral treatment. * Patients being unable tom comply with the protocol * Tumor stage T1 N0, T4 NX or TXNXM1b
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Histological Response (pCR) After Resection Than Chemotherapy Alone in Patients With Resectable Carcinoma of the Esophagus and Cardia. | Therapy followed in 14-16 weeks before surgery. After surgery the patients will be followed until 60 weeks after completed therapy. | Chireac tumour regression grade |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of Respective Neoadjuvant Therapies. | Five years follow up | Safety profile of carrying out radical surgery after respective neoadjuvant therapy. |
| HRQOL and Swallowing Function | Entry study up to Five years follow up | The European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 and disease specific questionnaires (QLQ-OES24/OG25). All items included in the questionnaires are analysed and also separate analysis of dysphagia questionnaires for oesophageal cancer were used, both clinically and psychometrically validated. All questions have four response alternatives (1, not at all; 2:a little, 3: quite a bit, 4: very much), except global scales which comprise seven response alternatives from poor to excellent. Questionnaire responses were transformed lineraly into scores ranging from 0 to 100 according to the EORTC scoring manual. A higher score indicates either more symotoms or better function, depending on the question. |
Countries
Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Radiochemotherapy Radiochemotherapy + Surgery
Radiochemotherapy: Cisplantin 100 mg/m2 day 1. 5-fluoracil 750 mg/m2/24 hours infusion day 1-5. Three cycles. In the chemoradiation arm the radiotherapy start week 4 and continuing until week 7. Dose adjustet according to current LPK and TPK values. | 90 |
| Chemotherapy Chemotherapy + surgery
Chemotherapy: Cisplantin 100 mg/m2 day 1. 5-fluoracil 750 mg/m2/24 hours infusion day 1-5. Three cycles. In the chemoradiation arm the radiotherapy start week 4 and continuing until week 7. Dose adjustet according to current LPK and TPK values.
Radiochemotherapy: Cisplantin 100 mg/m2 day 1. 5-fluoracil 750 mg/m2/24 hours infusion day 1-5. Three cycles. In the chemoradiation arm the radiotherapy start week 4 and continuing until week 7. Dose adjustet according to current LPK and TPK values. | 91 |
| Total | 181 |
Baseline characteristics
| Characteristic | Radiochemotherapy | Chemotherapy | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 38 Participants | 36 Participants | 74 Participants |
| Age, Categorical Between 18 and 65 years | 52 Participants | 55 Participants | 107 Participants |
| Region of Enrollment Sweden | 90 participants | 91 participants | 181 participants |
| Sex: Female, Male Female | 18 Participants | 14 Participants | 32 Participants |
| Sex: Female, Male Male | 72 Participants | 77 Participants | 149 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 90 | 0 / 91 |
| serious Total, serious adverse events | 57 / 90 | 41 / 91 |
Outcome results
Primary
Pathological Complete Histological Response (pCR) After Resection Than Chemotherapy Alone in Patients With Resectable Carcinoma of the Esophagus and Cardia.
Chireac tumour regression grade
Time frame: Therapy followed in 14-16 weeks before surgery. After surgery the patients will be followed until 60 weeks after completed therapy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiochemotherapy | Pathological Complete Histological Response (pCR) After Resection Than Chemotherapy Alone in Patients With Resectable Carcinoma of the Esophagus and Cardia. | 22 Participants |
| Chemotherapy | Pathological Complete Histological Response (pCR) After Resection Than Chemotherapy Alone in Patients With Resectable Carcinoma of the Esophagus and Cardia. | 7 Participants |
Secondary
HRQOL and Swallowing Function
The European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 and disease specific questionnaires (QLQ-OES24/OG25). All items included in the questionnaires are analysed and also separate analysis of dysphagia questionnaires for oesophageal cancer were used, both clinically and psychometrically validated. All questions have four response alternatives (1, not at all; 2:a little, 3: quite a bit, 4: very much), except global scales which comprise seven response alternatives from poor to excellent. Questionnaire responses were transformed lineraly into scores ranging from 0 to 100 according to the EORTC scoring manual. A higher score indicates either more symotoms or better function, depending on the question.
Time frame: Entry study up to Five years follow up
Population: Number of patients who responded to quality of Life instruments the EORTC QLQ-C30 and the oesophageal specific instrument
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Radiochemotherapy | HRQOL and Swallowing Function | Mean global QoL | 67 units on a scale |
| Radiochemotherapy | HRQOL and Swallowing Function | Dysphagia score all | 27 units on a scale |
| Chemotherapy | HRQOL and Swallowing Function | Mean global QoL | 69 units on a scale |
| Chemotherapy | HRQOL and Swallowing Function | Dysphagia score all | 31 units on a scale |
Secondary
Safety of Respective Neoadjuvant Therapies.
Safety profile of carrying out radical surgery after respective neoadjuvant therapy.
Time frame: Five years follow up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiochemotherapy | Safety of Respective Neoadjuvant Therapies. | 79 Participants |
| Chemotherapy | Safety of Respective Neoadjuvant Therapies. | 81 Participants |