Probiotic Therapy in Preventing Gastrointestinal Complications in Patients Undergoing Chemotherapy and Pelvic Radiation Therapy
Probiotic Therapy in Preventing Gastrointestinal Complications in Patients Undergoing Chemotherapy and Pelvic Radiation Therapy
RATIONALE: Probiotic therapy may reduce or prevent gastrointestinal complications in patients
 undergoing chemotherapy and pelvic radiation therapy.

 PURPOSE: This randomized phase III trial is studying how well probiotic therapy works in
 preventing gastrointestinal complications in patients undergoing chemotherapy and pelvic
 radiation therapy.
OBJECTIVES:

 Primary

 -  To determine whether live freeze-dried lactic acid bacteria probiotic (VSL#3®) is
 effective in reducing the acute treatment-related bowel function disturbances, as
 measured by the FACIT-D diarrhea subscale score in patients receiving concurrent
 chemotherapy and pelvic RT as adjuvant or primary treatment for malignancy.

 Secondary

 -  To determine whether VSL#3® can reduce chronic treatment-related bowel dysfunction
 following completion of therapy.

 -  To examine whether VSL#3® appears to have an impact on disease-free survival.

 -  To bank blood products for future studies. (exploratory)

 -  To characterize changes in the fecal microbiota and examine for correlation with
 treatment assignment and symptom scores. (exploratory)

 OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are
 stratified according to site of primary tumor (rectum/anus vs other), history of anterior
 resection of the rectum (yes vs no), total planned cumulative dose (including boost of
 external-beam radiotherapy [RT] or brachytherapy) (4,500-5,350 cGy vs > 5,350 cGy), and use
 of intensity-modulated RT [IMRT] for pelvic RT (yes vs no). Patients are randomized to 1 of 2
 treatment arms.

 -  Arm I: Patients receive live freeze-dried lactic acid bacteria probiotic (VSL#3®) orally
 (PO) 3 times a day during RT (5-8 weeks) and for 2 weeks after completion of RT.

 -  Arm II: Patients receive placebo PO 3 times a day during RT (5-8 weeks) and for 2 weeks
 after completion of RT.

 Patients self-report symptoms using the FACIT-D, PBFQ, PRO-CTCAE, and Uniscale/fatigue weekly
 during RT, for 2 weeks after completion of RT, and at 12 months following the completion of
 RT.

 Blood and stool samples may be collected from some patients for correlative studies.
DISEASE CHARACTERISTICS:

 -  Current diagnosis of cancer that supports the use of continuous definitive or adjuvant
 external-beam radiotherapy (RT) to the pelvis to a minimum dose of 4,500 cGy with the
 following parameters:

 -  The pelvis must be encompassed by the planned RT fields

 -  The superior border may not lie inferior to the most inferior aspect of the
 sacroiliac joints

 -  Portions of the rectum may have special blocking, depending upon disease
 site

 -  The total prescription dose must lie between 4,500-5,350 cGy (inclusive)

 -  A boost to primary tumor or tumor bed may be planned

 -  Planned treatment is to be given 4-5 times per week on a one- treatment-per-day
 basis

 -  The daily prescribed dose must lie between 170-210 cGy (inclusive) per day

 -  No planned split-course RT

 -  No proton RT

 -  Will receive concurrent administration of chemotherapy (fluorouracil, capecitabine,
 cisplatin, oxaliplatin, carboplatin, and/or mitomycin C) during pelvic RT

 -  No current or prior metastases beyond regional lymph nodes

 PATIENT CHARACTERISTICS:

 -  ECOG performance status (PS) of 0, 1, or 2

 -  Life expectancy ≥ 6 months

 -  Able to complete questionnaire(s) by themselves or with assistance

 -  Not pregnant or nursing

 -  Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing
 potential only

 -  Fertile patients must use effective contraception

 -  Hemoglobin > 10.0 g/dL

 -  White blood cells (WBC) > 3,500/mm³

 -  Absolute neutrophil count (ANC) > 1,500/mm³

 -  Platelet count > 100,000/mm³

 -  Willing to abstain from ingestion of yogurt products and/or any product containing
 probiotics during study drug treatment

 -  No known allergy to a probiotic preparation

 -  No history of inflammatory bowel disease

 -  No ≥ grade 3 diarrhea, ≥ grade 3 rectal bleeding, abdominal cramping, or incontinence
 of stool ≤ 7 days prior to registration

 -  No medical condition that may interfere with ability to receive protocol treatment

 -  No history of gastrointestinal or genitourinary obstruction or porphyria

 -  No history of irritable bowel syndrome (IBS)

 PRIOR CONCURRENT THERAPY:

 -  See Disease Characteristics

 -  No prior abdominal-perineal resection, Hartmann procedure, or other surgical procedure
 leaving the patient without a functioning rectum

 -  No planned use of leucovorin

 -  No prior pelvic RT

 -  No use of probiotics ≤ 2 weeks prior to registration

 -  No use of antibiotics ≤ 3 days prior to registration

 -  No planned continuous antibiotic treatment during RT