Cancer
Conditions
Keywords
Vitamin B-12, Vitamin B-6, Chemotherapy-Induced Neuropathy, Taxanes, Vinca alkaloid, Heavy metals, Neuropathy, Nerve pain
Brief summary
Many types of chemotherapy may cause nerve damage as a side effect. This neurotoxicity can manifest as peripheral sensory neuropathy (characterized by numbness, tingling, or pain). The goal of this study is to determine the efficacy of the combination of vitamin B6 and B12 in preventing chemotherapy induced neuropathy.
Detailed description
Neuropathy can be a significant side effect of chemotherapy using platinum compounds, taxanes, and vinca alkaloids. There is clinical and preclinical data that vitamin B6 and B12 may alleviate neuropathy in experimentally induced neuropathy in animal models, or clinical neuropathy such as diabetic neuropathy. This is a randomized phase III study of the use of multivitamins with or without vitamin B6 and B12 to prevent or relieve neuropathic toxicity from chemotherapy in patients receiving chemotherapy. Patients will be stratified by type of chemotherapy agent (3 groups), presence or absence of neuropathy at baseline, and randomized to receive placebo or vitamin B6/B12 supplementation.
Interventions
DIETARY_SUPPLEMENTMultivitamin (MV)
Multivitamins containing no more than 10 mg of pyridoxine and/or 10 micrograms of Vitamin B12 will be given to the patients on this arm.
DIETARY_SUPPLEMENTMultivitamin + Vitamin B12 + Vitamin B6
Multivitamin (containing no more than 10 mg of pyridoxine and/or 10 micrograms of Vitamin B12), plus Vitamin B6 tablets and Vitamin B12 injections
DRUGChemotherapy
Patients are treated per standard of care according to the choice of the treating physician with heavy metals (cisplatin, oxaliplatin), taxanes (paclitaxel, docetaxel), or vinca alkaloids (vincristine, vinorelbine) Ranges of cumulative doses (in mg/m2) are: paclitaxel, 700-960; docetaxel, 240-400; vincristine, 8-16; vinorelbine, 360-480; cisplatin, 240-400; oxaliplatin, 400-800; abraxane, 1200-1800
Sponsors
New Mexico Cancer Research Alliance
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. All patients, 18 years of age or older, with a cancer treated with any of the following drugs are eligible: * Taxanes, vinca alkaloid analogs, heavy metals. * Each patient will be allocated to the following 3 groups: * Group 1 (Heavy metals): Patients treated with cisplatin (\>25 mg/m2/week dose intensity) or oxaliplatin * Group 2 (Taxane): Patients treated with paclitaxel, docetaxel or abraxane * Group 3 (Vinca alkaloids): Patients treated with vincristine and vinorelbine. 2. Patients must have a life expectancy of at least 24 weeks. 3. Patients must have a Zubrod performance status of 0-2. 4. Patients must sign an informed consent. 5. Patients may have a grade 0 (chemotherapy naive) or 1 neuropathy (history of prior chemotherapy) prior to entry.
Exclusion criteria
1. Patients with symptomatic brain metastases are excluded from this study. 2. Pregnant women or nursing mothers are not eligible for this trial. Patients of child bearing potential must use adequate contraception. 3. Patients may receive no other concurrent complementary medicines during this study. 4. Patients with neuropathy induced diabetes are not eligible for this study 5. Patients with severe medical problems such as uncontrolled diabetes mellitus or cardiovascular disease or active infections are not eligible for this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neurotoxicity Assessment at Baseline | At study start; prior to treatment (week 0) | Neurotoxicity is evaluated using The Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) questionnaire. FACT-Tax is a validated, self-reported instrument. The questionnaire consists of 11 questions and possible scores for each question range from 0 (no neurotoxicity symptoms) to 4 (worst possible neurotoxicity symptoms). The total score for any patient can therefore range from 0 to 44. The questionnaire is given to patients to fill out at baseline (prior to chemotherapy treatment) and the mean total score for all patients is reported. |
| Neurotoxicity Assessment at Cycle 2 | 2 weeks | Neurotoxicity is evaluated using The Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) questionnaire. FACT-Tax is a validated, self-reported instrument. The questionnaire consists of 11 questions and possible scores for each question range from 0 (no neurotoxicity symptoms) to 4 (worst possible neurotoxicity symptoms). The total score for any patient can therefore range from 0 to 44. The questionnaire is given to patients to complete at completion of cycle 2 of chemotherapy treatment and the mean total score for all patients is reported. |
| Neurotoxicity Assessment at Cycle 4 | 4 weeks | Neurotoxicity is evaluated using The Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) questionnaire. FACT-Tax is a validated, self-reported instrument. The questionnaire consists of 16 questions and possible scores for each question range from 0 (no neurotoxicity symptoms) to 4 (worst possible neurotoxicity symptoms). The total score for any patient can therefore range from 0 to 44. The questionnaire is given to patients to fill out at completion of cycle 4 of their chemotherapy treatment and the mean total score for all patients is reported. |
| Change in Neurotoxicity Assessment Between Cycle 4 and Baseline | 4 weeks | Neurotoxicity is evaluated using The Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) questionnaire. FACT-Tax is a validated, self-reported instrument. The questionnaire consists of 11 questions and possible scores for each question range from 0 (no neurotoxicity symptoms) to 4 (worst possible neurotoxicity symptoms). The total score for any patient can therefore range from 0 to 44. The questionnaire is given to patients to fill out at baseline, cycle 2, and cycle 4 of their chemotherapy treatment. Change in neurotoxicity scores from baseline to the completion of 4 cycles are reported as the mean total score for all patients. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited between July, 2006, and September, 2013, at participating cancer clinics across the state of New Mexico
Participants by arm
| Arm | Count |
|---|---|
| Multivitamin (MV) Multivitamin only
Multivitamin (MV): Multivitamins containing no more than 10 mg of pyridoxine and/or 10 micrograms of Vitamin B12 will be given to the patients on this arm.
1 multivitamin pill will be taken orally, daily starting on the first day of chemotherapy and continuing for no more than 30 days past the cumulative chemotherapy dose (until the next cycle starts) | 157 |
| Multivitamin + Vitamin B12 + Vitamin B6 Multivitamin, plus Vitamin B6 tablets and Vitamin B12 injections
Multivitamin + Vitamin B12 + Vitamin B6: As in Arm 1, one multivitamin pill will be taken orally, daily starting on the first day of chemotherapy and continuing for no more than 30 days past the cumulative chemotherapy dose (until the next cycle starts).
The patient will also take the following, starting on the first day of chemotherapy:
1. pyridoxine 50 mg three times per day, orally and continue for no more than 30 days past the cumulative chemotherapy dose (until the next cycle starts)
2. Vitamin B12 one mg injected intramuscularly, every 3 or 4 weeks, depending on the timing of the chemotherapy for 4 doses.
Cumulative doses (in mg/m2) are:
paclitaxel, 700; docetaxel, 300; vincristine, 16; navelbine, 480; cisplatin, 300; oxaliplatin, 400 | 162 |
| Total | 319 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 1 |
Baseline characteristics
| Characteristic | Multivitamin (MV) | Multivitamin + Vitamin B12 + Vitamin B6 | Total |
|---|---|---|---|
| Age, Continuous | 56 years | 54.5 years | 55 years |
| Region of Enrollment United States | 157 participants | 162 participants | 319 participants |
| Sex: Female, Male Female | 114 Participants | 116 Participants | 230 Participants |
| Sex: Female, Male Male | 43 Participants | 46 Participants | 89 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 157 | 0 / 162 |
Outcome results
Primary
Change in Neurotoxicity Assessment Between Cycle 4 and Baseline
Neurotoxicity is evaluated using The Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) questionnaire. FACT-Tax is a validated, self-reported instrument. The questionnaire consists of 11 questions and possible scores for each question range from 0 (no neurotoxicity symptoms) to 4 (worst possible neurotoxicity symptoms). The total score for any patient can therefore range from 0 to 44. The questionnaire is given to patients to fill out at baseline, cycle 2, and cycle 4 of their chemotherapy treatment. Change in neurotoxicity scores from baseline to the completion of 4 cycles are reported as the mean total score for all patients.
Time frame: 4 weeks
Population: Of the 92 \& 97 patients in the Multivitamin (MV) and MV + Vit.B12 + VitB6 arms, 54 \& 62, respectively, in Group 1 (Taxanes) completed both 4 cycles of chemo and the FACT-Tax questionnaire at baseline and cycle 4; analysis is presented here. The same applies to 28 \& 20 patients in Group 2 (Heavy Metals) and 5 \& 9 patients in Group 3 (Vinca)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Taxane Group: Multivitamin (MV) Arm | Change in Neurotoxicity Assessment Between Cycle 4 and Baseline | 7.0 units on a scale | Standard Deviation 9.9 |
| Taxane Group: MV + Vitamin B12 + Vitamin B6 | Change in Neurotoxicity Assessment Between Cycle 4 and Baseline | 7.2 units on a scale | Standard Deviation 9.8 |
| Heavy Metals Group: Multivitamin (MV) Arm | Change in Neurotoxicity Assessment Between Cycle 4 and Baseline | 3.9 units on a scale | Standard Deviation 7.1 |
| Heavy Metals Group: MV + Vitamin B12 + Vitamin B6 Arm | Change in Neurotoxicity Assessment Between Cycle 4 and Baseline | 4.7 units on a scale | Standard Deviation 5.7 |
| Vinca Alkaloids Group: Multivitamin (MV) Arm | Change in Neurotoxicity Assessment Between Cycle 4 and Baseline | 11.8 units on a scale | Standard Deviation 4.7 |
| Vinca Alkaloids Group: MV + Vitamin B12 + Vitamin B6 Arm | Change in Neurotoxicity Assessment Between Cycle 4 and Baseline | 7 units on a scale | Standard Deviation 9.2 |
p-value: 0.91ANOVA
Primary
Neurotoxicity Assessment at Baseline
Neurotoxicity is evaluated using The Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) questionnaire. FACT-Tax is a validated, self-reported instrument. The questionnaire consists of 11 questions and possible scores for each question range from 0 (no neurotoxicity symptoms) to 4 (worst possible neurotoxicity symptoms). The total score for any patient can therefore range from 0 to 44. The questionnaire is given to patients to fill out at baseline (prior to chemotherapy treatment) and the mean total score for all patients is reported.
Time frame: At study start; prior to treatment (week 0)
Population: Of the 92 and 97 patients in the MV arm and MV + Vit.B12 + VitB6 arm, 84 and 86 patients, respectively, in the Group 1 (Taxanes) completed the FACT-Tax questionnaire at baseline and the analysis is presented here. This also applies to 48 and 45 patients in Group 2 (Heavy Metals) and 10 and 12 patients in Group 3 (Vincas)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Taxane Group: Multivitamin (MV) Arm | Neurotoxicity Assessment at Baseline | 8.5 units on a scale | Standard Deviation 8.5 |
| Taxane Group: MV + Vitamin B12 + Vitamin B6 | Neurotoxicity Assessment at Baseline | 7.3 units on a scale | Standard Deviation 7.3 |
| Heavy Metals Group: Multivitamin (MV) Arm | Neurotoxicity Assessment at Baseline | 5.23 units on a scale | Standard Deviation 5.86 |
| Heavy Metals Group: MV + Vitamin B12 + Vitamin B6 Arm | Neurotoxicity Assessment at Baseline | 4.58 units on a scale | Standard Deviation 5.34 |
| Vinca Alkaloids Group: Multivitamin (MV) Arm | Neurotoxicity Assessment at Baseline | 6.80 units on a scale | Standard Deviation 5.09 |
| Vinca Alkaloids Group: MV + Vitamin B12 + Vitamin B6 Arm | Neurotoxicity Assessment at Baseline | 2.08 units on a scale | Standard Deviation 2.02 |
Primary
Neurotoxicity Assessment at Cycle 2
Neurotoxicity is evaluated using The Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) questionnaire. FACT-Tax is a validated, self-reported instrument. The questionnaire consists of 11 questions and possible scores for each question range from 0 (no neurotoxicity symptoms) to 4 (worst possible neurotoxicity symptoms). The total score for any patient can therefore range from 0 to 44. The questionnaire is given to patients to complete at completion of cycle 2 of chemotherapy treatment and the mean total score for all patients is reported.
Time frame: 2 weeks
Population: Of the 92 \& 97 patients in the MV and MV + Vit.B12 + VitB6 arms, 72 \& 80 patients, respectively, in the Group 1 (Taxanes) both completed 2 cycles of treatment and completed the FACT-Tax questionnaire at cycle 2, and the analysis is presented here. The same applies to 27 \& 25 patients in Group 2 (Heavy Metals) and 9 \& 10 patients in Group 3 (Vinca)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Taxane Group: Multivitamin (MV) Arm | Neurotoxicity Assessment at Cycle 2 | 13.0 units on a scale | Standard Deviation 10.9 |
| Taxane Group: MV + Vitamin B12 + Vitamin B6 | Neurotoxicity Assessment at Cycle 2 | 12.0 units on a scale | Standard Deviation 9.9 |
| Heavy Metals Group: Multivitamin (MV) Arm | Neurotoxicity Assessment at Cycle 2 | 9.7 units on a scale | Standard Deviation 5.99 |
| Heavy Metals Group: MV + Vitamin B12 + Vitamin B6 Arm | Neurotoxicity Assessment at Cycle 2 | 8.4 units on a scale | Standard Deviation 7.16 |
| Vinca Alkaloids Group: Multivitamin (MV) Arm | Neurotoxicity Assessment at Cycle 2 | 14.56 units on a scale | Standard Deviation 12.9 |
| Vinca Alkaloids Group: MV + Vitamin B12 + Vitamin B6 Arm | Neurotoxicity Assessment at Cycle 2 | 5.6 units on a scale | Standard Deviation 6.59 |
Primary
Neurotoxicity Assessment at Cycle 4
Neurotoxicity is evaluated using The Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) questionnaire. FACT-Tax is a validated, self-reported instrument. The questionnaire consists of 16 questions and possible scores for each question range from 0 (no neurotoxicity symptoms) to 4 (worst possible neurotoxicity symptoms). The total score for any patient can therefore range from 0 to 44. The questionnaire is given to patients to fill out at completion of cycle 4 of their chemotherapy treatment and the mean total score for all patients is reported.
Time frame: 4 weeks
Population: Of the 92 \& 97 patients in the MV and MV + Vit.B12 + VitB6 arms, 57 \& 65 patients, respectively, in Group 1 (Taxanes) completed both 4 cycles of chemotherapy and completed the FACT-Tax questionnaire at cycle 4, and the analysis is presented here. The same applies to 28 \& 21 patients in Group 2 (Heavy Metals) and 6 \& 9 patients in Group 3 (Vinca)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Taxane Group: Multivitamin (MV) Arm | Neurotoxicity Assessment at Cycle 4 | 14.5 units on a scale | Standard Deviation 11.4 |
| Taxane Group: MV + Vitamin B12 + Vitamin B6 | Neurotoxicity Assessment at Cycle 4 | 14.5 units on a scale | Standard Deviation 11.1 |
| Heavy Metals Group: Multivitamin (MV) Arm | Neurotoxicity Assessment at Cycle 4 | 8.71 units on a scale | Standard Deviation 6.5 |
| Heavy Metals Group: MV + Vitamin B12 + Vitamin B6 Arm | Neurotoxicity Assessment at Cycle 4 | 7.05 units on a scale | Standard Deviation 6.55 |
| Vinca Alkaloids Group: Multivitamin (MV) Arm | Neurotoxicity Assessment at Cycle 4 | 17.5 units on a scale | Standard Deviation 5.36 |
| Vinca Alkaloids Group: MV + Vitamin B12 + Vitamin B6 Arm | Neurotoxicity Assessment at Cycle 4 | 9.22 units on a scale | Standard Deviation 10.22 |