Probiotic Therapy in Preventing Gastrointestinal Complications in Patients Undergoing Chemotherapy and Pelvic Radiation Therapy

A Phase III, Randomized, Double-Blind Placebo Controlled Study of the Probiotic Preparation VSL#3® Versus Placebo in the Prevention of Acute Enteritis in Patients Receiving Concurrent 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