Oral diindolylmethane (DIM)

Pilot evaluation of a nonsurgical treatment for cervical dysplasia

Giuseppe Del Priore, Deleep Kumar Gudipudi, Nadine Montemarano, Antonella M. Restivo, Jeanetta Malanowska-Stega, Alan A. Arslan

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Objective: Standard surgical treatment for CIN may impair fertility generating a need for alternative treatment options. We tested the efficacy and toxicity of oral DIM in the treatment of CIN 2 or 3 lesions. Methods: Patients with biopsy-proven cervical intraepithelial neoplasia (CIN) 2 or 3 scheduled for loop electrosurgical excision procedure (LEEP) were randomized 2:1 to receive diindolylmethane (DIM) (BioResponse-DIM®, BioResponse, Boulder, CO) orally at approximately 2 mg/kg/day for 12 weeks or placebo (defatted rice bran, BioResponse). Subjects were evaluated every 3-4 months for 1 year. Analysis of data up to 1 year was assessed including Pap smear, HPV, colposcopy, biopsy and physical examination were performed at follow-up. Central pathology review confirmed all histology diagnoses. Results: To date, 64 subjects (mean age 28 years, range 18-61) have been enrolled (45 in the DIM arm, 19 in the placebo arm), with 60 available for analysis. Average follow-up was 6 months. At enrollment, 58% were diagnosed with CIN 2 and 42% with CIN 3, 57% of subjects were Caucasian, 15% African American, 12% Hispanic and 17% Asian. During treatment 2 subjects (3%) complained of nausea (grade 2) at the 3- to 4-month visit. No systemic toxicities were observed (normal CBC, LFTs, comprehensive metabolic). Forty-six subjects had biopsies at first follow-up (77%). Twenty-one subjects (47%) in the DIM group had improved CIN with a decrease by 1-2 grades or a normal result. Median time to improvement was 5 months. Improved Pap smear was seen in 49% (22/45) with either a less severe abnormality or normal result. Colposcopy improved in twenty-five subjects in the DIM group (56%). Of these 25 subjects, 21 (84%) had improved colposcopic impression, 13 (52%) had a decrease in involved quadrants and 18 (72%) had a decrease in lesion number. Complete colposcopic response was observed in 4 subjects (9%). Stratifying by level of dysplasia, age, race, HPV status, tobacco use, contraceptive used did not alter the results. At median follow-up of 6 months, 85% of subjects have not required LEEP based on routine clinical triage of improving global assessment. There was no statistically significant difference in any outcome between the DIM and placebo group. Conclusion: Oral DIM at 2 mg/kg/day is well tolerated with no significant toxicity. We observed a high rate of clinically significant improvement in confirmed CIN 2 or 3 lesions among both treatment groups in this randomized clinical trial.

Original languageEnglish
Pages (from-to)464-467
Number of pages4
JournalGynecologic Oncology
Volume116
Issue number3
DOIs
StatePublished - Mar 2010

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Uterine Cervical Dysplasia
Cervical Intraepithelial Neoplasia
Papanicolaou Test
Colposcopy
Placebos
Therapeutics
Biopsy
diindolylmethane
Triage
Tobacco Use
Carbon Monoxide
Contraceptive Agents
Hispanic Americans
African Americans
Nausea
Physical Examination
Fertility
Histology
Randomized Controlled Trials
Pathology

Keywords

  • Cervix
  • Diindolylmethane
  • Dysplasia

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Del Priore, G., Gudipudi, D. K., Montemarano, N., Restivo, A. M., Malanowska-Stega, J., & Arslan, A. A. (2010). Oral diindolylmethane (DIM): Pilot evaluation of a nonsurgical treatment for cervical dysplasia. Gynecologic Oncology, 116(3), 464-467. https://doi.org/10.1016/j.ygyno.2009.10.060

Oral diindolylmethane (DIM) : Pilot evaluation of a nonsurgical treatment for cervical dysplasia. / Del Priore, Giuseppe; Gudipudi, Deleep Kumar; Montemarano, Nadine; Restivo, Antonella M.; Malanowska-Stega, Jeanetta; Arslan, Alan A.

In: Gynecologic Oncology, Vol. 116, No. 3, 03.2010, p. 464-467.

Research output: Contribution to journalArticle

Del Priore, G, Gudipudi, DK, Montemarano, N, Restivo, AM, Malanowska-Stega, J & Arslan, AA 2010, 'Oral diindolylmethane (DIM): Pilot evaluation of a nonsurgical treatment for cervical dysplasia', Gynecologic Oncology, vol. 116, no. 3, pp. 464-467. https://doi.org/10.1016/j.ygyno.2009.10.060
Del Priore G, Gudipudi DK, Montemarano N, Restivo AM, Malanowska-Stega J, Arslan AA. Oral diindolylmethane (DIM): Pilot evaluation of a nonsurgical treatment for cervical dysplasia. Gynecologic Oncology. 2010 Mar;116(3):464-467. https://doi.org/10.1016/j.ygyno.2009.10.060
Del Priore, Giuseppe ; Gudipudi, Deleep Kumar ; Montemarano, Nadine ; Restivo, Antonella M. ; Malanowska-Stega, Jeanetta ; Arslan, Alan A. / Oral diindolylmethane (DIM) : Pilot evaluation of a nonsurgical treatment for cervical dysplasia. In: Gynecologic Oncology. 2010 ; Vol. 116, No. 3. pp. 464-467.
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abstract = "Objective: Standard surgical treatment for CIN may impair fertility generating a need for alternative treatment options. We tested the efficacy and toxicity of oral DIM in the treatment of CIN 2 or 3 lesions. Methods: Patients with biopsy-proven cervical intraepithelial neoplasia (CIN) 2 or 3 scheduled for loop electrosurgical excision procedure (LEEP) were randomized 2:1 to receive diindolylmethane (DIM) (BioResponse-DIM{\circledR}, BioResponse, Boulder, CO) orally at approximately 2 mg/kg/day for 12 weeks or placebo (defatted rice bran, BioResponse). Subjects were evaluated every 3-4 months for 1 year. Analysis of data up to 1 year was assessed including Pap smear, HPV, colposcopy, biopsy and physical examination were performed at follow-up. Central pathology review confirmed all histology diagnoses. Results: To date, 64 subjects (mean age 28 years, range 18-61) have been enrolled (45 in the DIM arm, 19 in the placebo arm), with 60 available for analysis. Average follow-up was 6 months. At enrollment, 58{\%} were diagnosed with CIN 2 and 42{\%} with CIN 3, 57{\%} of subjects were Caucasian, 15{\%} African American, 12{\%} Hispanic and 17{\%} Asian. During treatment 2 subjects (3{\%}) complained of nausea (grade 2) at the 3- to 4-month visit. No systemic toxicities were observed (normal CBC, LFTs, comprehensive metabolic). Forty-six subjects had biopsies at first follow-up (77{\%}). Twenty-one subjects (47{\%}) in the DIM group had improved CIN with a decrease by 1-2 grades or a normal result. Median time to improvement was 5 months. Improved Pap smear was seen in 49{\%} (22/45) with either a less severe abnormality or normal result. Colposcopy improved in twenty-five subjects in the DIM group (56{\%}). Of these 25 subjects, 21 (84{\%}) had improved colposcopic impression, 13 (52{\%}) had a decrease in involved quadrants and 18 (72{\%}) had a decrease in lesion number. Complete colposcopic response was observed in 4 subjects (9{\%}). Stratifying by level of dysplasia, age, race, HPV status, tobacco use, contraceptive used did not alter the results. At median follow-up of 6 months, 85{\%} of subjects have not required LEEP based on routine clinical triage of improving global assessment. There was no statistically significant difference in any outcome between the DIM and placebo group. Conclusion: Oral DIM at 2 mg/kg/day is well tolerated with no significant toxicity. We observed a high rate of clinically significant improvement in confirmed CIN 2 or 3 lesions among both treatment groups in this randomized clinical trial.",
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