Neoadjuvant Chemoradiation With 5-FU(or Capecitabine) and Oxaliplatin Combined With Hyperthermia in Rectal Cancer

This trial examines the feasibility, effectiveness and safety of a combination of radiotherapy (over a period of five weeks) and chemotherapy (with 5-FU or Capecitabine and Oxaliplatin) and 10 fractions of deep regional hyperthermia in patients with primary locally advanced or locally recurrent rectal cancer. Previous pelvic irradiation in case of a local recurrence is not excluded from the trial. The treatment protocol aims on a preoperatively improved tumor regression allowing less aggressive surgery in primary locally advanced rectal cancer and a higher rate of curative resections in heavily pretreated locally recurrent rectal cancers.

Primary endpoint of the trial is the feasibility rate of a multimodal regimen consisting of radiochemotherapy and hyperthermia. Secondary endpoints are local control, survival rates, and toxicity. It is planned to include a total number of 59 patients over a period of 2.5 years.


Eligibility Criteria:
Inclusion Criteria:

* Age ≥ 18 years
* Histologically confirmed, locally advanced or recurrent (any recurrence of tumor within the lesser pelvis; resectable or non-resectable) adenocarcinoma of the rectum (UICC stage IIB-IV); distant oligo-metastases may be present.
* ECOG-performance status \< 2
* Sufficient bone marrow function:
* WBC \> 3,5 x 10\^9/l
* Neutrophil granulocytes \> 1,5 x 10\^9/l
* Platelets \> 100 x 10\^9/l
* Hemoglobin \> 10 g/dl
* Sufficient liver function: Bilirubin \< 2,0 mg%, SGOT, SGPT, alkaline phosphatase, gGT less than 3 times upper limit of normal
* Serum creatinine \< 1,5 mg%, glomerular filtration rate (or comparable test) \> 50 ml/min
* Signed study-specific consent form prior to therapy
* Fertile patients must use effective contraception during and for 6 months after study treatment
* Considered fit for oxaliplatin and 5-FU-containing combination chemotherapy

Exclusion Criteria:

* Pelvic radiotherapy during the last 12 months
* Pregnant or lactating/nursing women
* Drug addiction
* On-treatment participation on other trials
* Active intractable or uncontrollable infection
* Prior or concurrent malignancy (≤ 5 years prior to enrolment in study) except rectal cancer or non-melanoma skin cancer or cervical carcinoma FIGO stage 0-1 if the patient is continuously disease-free
* Chronic diarrhea (\> NCI CTC-Grad 1)
* Chronic inflammatory disease of the intestine
* Collagen vascular disease
* The presence of congenital diseases with increased radiation sensitivity, for example teleangiectatic ataxia, or similar
* Pre-existing uncontrolled cardiac disease, signs of cardiac failure, or rhythm disturbances requiring therapy
* Myocardial infarction within the past 12 months
* Congestive heart failure
* Complete bundle branch block
* New York Heart Association (NYHA) class III or IV heart disease
* Known allergic reactions on study medication
* Cardiac pacemaker
* Disease that would preclude chemoradiation or deep regional hyperthermia
* Any metal implants (with exception of non-clustered marker clips)
* Psychological, familial, sociological, or geographical condition that would preclude study compliance
* Patients deemed technically unsatisfactory for deep regional hyperthermia
* Cardiac symptoms (\> NCI CTCAE Grade 1) due to pretreatment with fluoropyrimidines
* Neurological symptoms (\> NCI CTCAE Grade 1) due to pretreatment with oxaliplatin
* Rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
* Oral anticoagulation