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Published in: Radiation Oncology 1/2014

Open Access 01-12-2014 | Research

Hypericum perforatum and neem oil for the management of acute skin toxicity in head and neck cancer patients undergoing radiation or chemo-radiation: a single-arm prospective observational study

Authors: Pierfrancesco Franco, Ilenia Potenza, Francesco Moretto, Mattia Segantin, Mario Grosso, Antonello Lombardo, Daniela Taricco, Patrizia Vallario, Andrea Riccardo Filippi, Monica Rampino, Umberto Ricardi

Published in: Radiation Oncology | Issue 1/2014

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Abstract

Background

Radiation dermatitis is common in patients treated with combined radiotherapy and chemotherapy for head and neck malignancies. Its timely and adequate management is of uttermost importance for both oncological outcomes and global quality of life. We prospectively evaluated the role of hypericum perforatum and neem oil (Holoil®; RIMOS srl, Mirandola, Italy) in the treatment of acute skin toxicity for patients undergoing radiotherapy or chemo-radiotherapy for head and neck cancer.

Methods

A consecutive series of 28 head and neck cancer patients submitted to radiotherapy (RT) was enrolled onto this mono-institutional single-arm prospective observational study. Patients undergoing both definitive or post-operative radiotherapy were allowed, either as exclusive modality or combined with (concomitant or induction) chemotherapy. We started Holoil treatment whenever bright erythema, moderate oedema or patchy moist desquamation were observed. Holoil® was used during all RT course and during follow up time, until acute skin toxicity recovery.

Results

The maximum detected acute skin toxicity was Grade 1 in 7% of patients, Grade 2 in 68%, Grade 3 in 25%, while at the end of RT was Grade 0 in 3.5%, Grade 1 in 32%, Grade 2 in 61%, Grade 3 in 3.5%. For patients having G2 acute skin toxicity, it mainly started at weeks 4-5; for those having G3, it began during weeks 5-6. Median times spent with G2 or G3 toxicity were 17.5 and 11 days. Patients having G2 acute skin toxicity had a dermatitis worsening in 27% of case (median occurrence time: 7 days). G3 events were reconverted to a G2 profile in all patients (median time: 7 days). Those experiencing a G2 skin event were converted to a G1 score in 23% of cases (median time: 14 days). Time between maximum acute skin toxicity and complete skin recovery after RT was 27 days.

Conclusions

Holoil® proved to be a safe and active option in the management of acute skin toxicity in head and neck cancer patients submitted to RT or chemo-radiotherapy. A prophylactic effect in the prevention of moist desquamation may be hypothesized for hypericum and neem oil and need to be tested within a prospective controlled study.
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Literature
1.
go back to reference Hymes SR, Strom EA, Fife C: Radiation dermatitis: clinical presentation, pathophysiology, and treatment. J Am Acad Dermatol. 2006, 54 (1): 28-46. 10.1016/j.jaad.2005.08.054.CrossRefPubMed Hymes SR, Strom EA, Fife C: Radiation dermatitis: clinical presentation, pathophysiology, and treatment. J Am Acad Dermatol. 2006, 54 (1): 28-46. 10.1016/j.jaad.2005.08.054.CrossRefPubMed
2.
go back to reference Filippi AR, Franco P, Ricardi U: Is clinical radiosensitivity a complex genetically controlled event?. Tumori. 2006, 92 (2): 87-91.PubMed Filippi AR, Franco P, Ricardi U: Is clinical radiosensitivity a complex genetically controlled event?. Tumori. 2006, 92 (2): 87-91.PubMed
3.
go back to reference Numico G, Franco P, Cristofano A, Migliaccio F, Spinazze’ S, Silvestris N, Cante D, Sciacero P, La Porta MR, Girelli F, Ricardi U: Is the combination of Cetuximab with chemo-radiotherapy regimens worthwhile in the treatment of locally advanced head and neck cancer? A review of current evidence. Crit Rev Oncol Hematol. 2013, 85 (2): 112-120. 10.1016/j.critrevonc.2012.05.005.CrossRefPubMed Numico G, Franco P, Cristofano A, Migliaccio F, Spinazze’ S, Silvestris N, Cante D, Sciacero P, La Porta MR, Girelli F, Ricardi U: Is the combination of Cetuximab with chemo-radiotherapy regimens worthwhile in the treatment of locally advanced head and neck cancer? A review of current evidence. Crit Rev Oncol Hematol. 2013, 85 (2): 112-120. 10.1016/j.critrevonc.2012.05.005.CrossRefPubMed
4.
go back to reference Rampino M, Ricardi U, Munoz F, Reali A, Barone C, Musu AR, Balcet V, Franco P, Grillo R, Bustreo S, Pecorari G, Cavalot A, Garzino Demo P, Ciuffreda L, Ragona R, Schena M: Concomitant adjuvant chemo-radiotherapy with weekly low-dose cisplatin for high-risk squamous cell carcinoma of the head and neck: a phase II prospective trial. Clin Oncol. 2011, 23 (2): 134-140. 10.1016/j.clon.2010.09.004.CrossRef Rampino M, Ricardi U, Munoz F, Reali A, Barone C, Musu AR, Balcet V, Franco P, Grillo R, Bustreo S, Pecorari G, Cavalot A, Garzino Demo P, Ciuffreda L, Ragona R, Schena M: Concomitant adjuvant chemo-radiotherapy with weekly low-dose cisplatin for high-risk squamous cell carcinoma of the head and neck: a phase II prospective trial. Clin Oncol. 2011, 23 (2): 134-140. 10.1016/j.clon.2010.09.004.CrossRef
5.
go back to reference Koeberle A, Rossi A, Bauer J, Dehm F, Verotta L, Northoff H, Sautebin L, Werz O: Hyperforin, an anti-inflammatory constituent from St. John’s wort, inhibits microsomal prostaglandin E(2) synthase-1 and suppresses prostaglandin E(2) formation in vivo. Front Pharmacol. 2011, 2: 7-10.3389/fphar.2011.00007.PubMedCentralCrossRefPubMed Koeberle A, Rossi A, Bauer J, Dehm F, Verotta L, Northoff H, Sautebin L, Werz O: Hyperforin, an anti-inflammatory constituent from St. John’s wort, inhibits microsomal prostaglandin E(2) synthase-1 and suppresses prostaglandin E(2) formation in vivo. Front Pharmacol. 2011, 2: 7-10.3389/fphar.2011.00007.PubMedCentralCrossRefPubMed
6.
go back to reference Narayanan AS, Raja SS, Ponmurugan K, Kandekar SC, Natarajaseenivasan K, Maripandi A, Mandeel QA: Antibacterial activity of selected medicinal plants against multiple antibiotic resistant uropathogens: a study from Kolli Hills, Tamil Nadu. India Benef Microbes. 2011, 2 (3): 235-243. 10.3920/BM2010.0033.CrossRefPubMed Narayanan AS, Raja SS, Ponmurugan K, Kandekar SC, Natarajaseenivasan K, Maripandi A, Mandeel QA: Antibacterial activity of selected medicinal plants against multiple antibiotic resistant uropathogens: a study from Kolli Hills, Tamil Nadu. India Benef Microbes. 2011, 2 (3): 235-243. 10.3920/BM2010.0033.CrossRefPubMed
7.
go back to reference Cante D, La Porta MR, Franco P, Sciacero P, Girelli GF, Marra A, Numico G, Denaro N, Russi EG, Ricardi U: Management of ‘in-field’ skin toxicity in head and neck cancer patients treated with combined cetuximab and radiotherapy. Oncology. 2013, 85 (5): 257-261. 10.1159/000355579.CrossRefPubMed Cante D, La Porta MR, Franco P, Sciacero P, Girelli GF, Marra A, Numico G, Denaro N, Russi EG, Ricardi U: Management of ‘in-field’ skin toxicity in head and neck cancer patients treated with combined cetuximab and radiotherapy. Oncology. 2013, 85 (5): 257-261. 10.1159/000355579.CrossRefPubMed
8.
go back to reference Russi EG, Merlano MC, Numico G, Corvo’ R, Benasso M, Vigna-Taglianti R, Melano A, Denaro N, Pergolizzi S, Colantonio I, Lucio F, Brizio F, Ricardi U: The effects on pain and activity of daily living caused by crusted exudation in patients with head and neck cancer treated with cetuximab and radiotherapy. Support Care Cancer. 2012, 20 (9): 2141-2147. 10.1007/s00520-011-1324-4.CrossRefPubMed Russi EG, Merlano MC, Numico G, Corvo’ R, Benasso M, Vigna-Taglianti R, Melano A, Denaro N, Pergolizzi S, Colantonio I, Lucio F, Brizio F, Ricardi U: The effects on pain and activity of daily living caused by crusted exudation in patients with head and neck cancer treated with cetuximab and radiotherapy. Support Care Cancer. 2012, 20 (9): 2141-2147. 10.1007/s00520-011-1324-4.CrossRefPubMed
9.
go back to reference Russi EG, Bensadoun RJ, Merlano MC, Bourhis J, Ricardi U, Giralt J, Pinto C, Budach W, Corvo’ R, Lacouture ME, Bernier J: Bio-radiation dermatitis: the need of a new grading: in regard to Bernier et al.: Ann Oncol 2011, 22(10): 2191–2200. Ann Oncol. 2013, 24 (9): 2463-2465. 10.1093/annonc/mdt281.CrossRefPubMed Russi EG, Bensadoun RJ, Merlano MC, Bourhis J, Ricardi U, Giralt J, Pinto C, Budach W, Corvo’ R, Lacouture ME, Bernier J: Bio-radiation dermatitis: the need of a new grading: in regard to Bernier et al.: Ann Oncol 2011, 22(10): 2191–2200. Ann Oncol. 2013, 24 (9): 2463-2465. 10.1093/annonc/mdt281.CrossRefPubMed
10.
go back to reference Cox JD, Stetz J, Pajak TF: Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995, 31 (5): 1341-1346. 10.1016/0360-3016(95)00060-C.CrossRefPubMed Cox JD, Stetz J, Pajak TF: Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995, 31 (5): 1341-1346. 10.1016/0360-3016(95)00060-C.CrossRefPubMed
11.
go back to reference McQuestion M: Evidence-based skin care management in radiation therapy. Semin Oncol Nurs. 2006, 22 (3): 163-173. 10.1016/j.soncn.2006.04.004.CrossRefPubMed McQuestion M: Evidence-based skin care management in radiation therapy. Semin Oncol Nurs. 2006, 22 (3): 163-173. 10.1016/j.soncn.2006.04.004.CrossRefPubMed
12.
go back to reference Bernier J, Russi EG, Homey B, Merlano MC, Mesia R, Peyrade F, Budach W: Management of radiation dermatitis in patients receiving cetuximab and radiotherapy for locally advanced squamous cell carcinoma of the head and neck: proposal for a revised grading system and consensus management guidelines. Ann Oncol. 2011, 22 (10): 2191-2200. 10.1093/annonc/mdr139.CrossRefPubMed Bernier J, Russi EG, Homey B, Merlano MC, Mesia R, Peyrade F, Budach W: Management of radiation dermatitis in patients receiving cetuximab and radiotherapy for locally advanced squamous cell carcinoma of the head and neck: proposal for a revised grading system and consensus management guidelines. Ann Oncol. 2011, 22 (10): 2191-2200. 10.1093/annonc/mdr139.CrossRefPubMed
13.
go back to reference Russi EG, Merlano MC, Comino A, Numico G: Ultrathin hydrocolloid dressing in skin damaged from alternating radiotherapy and chemotherapy plus cetuximab in advanced head and neck cancer (G.O.N.O. AlteRCC Italian Trial): in regard to Macmillan et al. (Int J Radiat Oncol Biol Phys 2007;68:864–872). Int J Radiat Oncol Biol Phys. 2007, 69 (2): 638-639. 10.1016/j.ijrobp.2007.05.063.CrossRefPubMed Russi EG, Merlano MC, Comino A, Numico G: Ultrathin hydrocolloid dressing in skin damaged from alternating radiotherapy and chemotherapy plus cetuximab in advanced head and neck cancer (G.O.N.O. AlteRCC Italian Trial): in regard to Macmillan et al. (Int J Radiat Oncol Biol Phys 2007;68:864–872). Int J Radiat Oncol Biol Phys. 2007, 69 (2): 638-639. 10.1016/j.ijrobp.2007.05.063.CrossRefPubMed
14.
go back to reference Greeson JM, Sanford B, Monti DA: St. John’s wort (Hypericum perforatum): a review of the current pharmacological, toxicological, and clinical literature. Psychopharmacology (Berl). 2001, 153 (4): 402-414. 10.1007/s002130000625.CrossRef Greeson JM, Sanford B, Monti DA: St. John’s wort (Hypericum perforatum): a review of the current pharmacological, toxicological, and clinical literature. Psychopharmacology (Berl). 2001, 153 (4): 402-414. 10.1007/s002130000625.CrossRef
15.
go back to reference Schempp CM, Kirkin V, Simon-Haarhaus B, Kersten A, Kiss J, Termeer CC, Gilb B, Kaufmann T, Borner C, Sleeman JP, Simon JC: Inhibition of tumour cell growth by hyperforin, a novel anticancer drug from St. John’s wort that acts by induction of apoptosis. Oncogene. 2002, 21 (8): 1242-1250. 10.1038/sj.onc.1205190.CrossRefPubMed Schempp CM, Kirkin V, Simon-Haarhaus B, Kersten A, Kiss J, Termeer CC, Gilb B, Kaufmann T, Borner C, Sleeman JP, Simon JC: Inhibition of tumour cell growth by hyperforin, a novel anticancer drug from St. John’s wort that acts by induction of apoptosis. Oncogene. 2002, 21 (8): 1242-1250. 10.1038/sj.onc.1205190.CrossRefPubMed
16.
go back to reference Hostanska K, Reichling J, Bommer S, Weber M, Saller R: Hyperforin a constituent of St.John’s wort (Hypericum perforatum L.) extract induces apoptosis by triggering activation of caspases and with hypericin synergistically exerts cytotoxicity towards human malignant cell lines. Eur J Pharm Biopharm. 2003, 56 (1): 121-132. 10.1016/S0939-6411(03)00046-8.CrossRefPubMed Hostanska K, Reichling J, Bommer S, Weber M, Saller R: Hyperforin a constituent of St.John’s wort (Hypericum perforatum L.) extract induces apoptosis by triggering activation of caspases and with hypericin synergistically exerts cytotoxicity towards human malignant cell lines. Eur J Pharm Biopharm. 2003, 56 (1): 121-132. 10.1016/S0939-6411(03)00046-8.CrossRefPubMed
17.
go back to reference Dona M, Dell’Aica I, Pezzato E, Sartor L, Calabrese F, Della Barbera M, Donella-Deana A, Appendino G, Borsarini A, Caniato R, Garbisa S: Hyperforin inhibits cancer invasion and metastasis. Cancer Res. 2004, 64 (17): 6225-6232. 10.1158/0008-5472.CAN-04-0280.CrossRefPubMed Dona M, Dell’Aica I, Pezzato E, Sartor L, Calabrese F, Della Barbera M, Donella-Deana A, Appendino G, Borsarini A, Caniato R, Garbisa S: Hyperforin inhibits cancer invasion and metastasis. Cancer Res. 2004, 64 (17): 6225-6232. 10.1158/0008-5472.CAN-04-0280.CrossRefPubMed
18.
go back to reference Martınez-Poveda B, Quesada AR, Medina MA: Hyperforin, a bio-active compound of St.John’s Wort, is a new inhibitor of angiogenesis targeting several key steps of the process. Int J Cancer. 2005, 117 (5): 775-780. 10.1002/ijc.21246.CrossRefPubMed Martınez-Poveda B, Quesada AR, Medina MA: Hyperforin, a bio-active compound of St.John’s Wort, is a new inhibitor of angiogenesis targeting several key steps of the process. Int J Cancer. 2005, 117 (5): 775-780. 10.1002/ijc.21246.CrossRefPubMed
19.
go back to reference Santos dos AC, Rodrigues OG, de Araojo LV, Dos Santos SB, de C Guerra RM, Feitosa ML, Whaubtyfran CT, Santos-Ribeiro A: Use of neem extract in the control of acariasis by Myobia musculi Schranck (Acari: Miobidae) and Myocoptes musculinus Koch (Acari: Listrophoridae) in mice (Mus musculus var. albina L.). Neotrop Entomol. 2006, 35 (2): 269-272. Santos dos AC, Rodrigues OG, de Araojo LV, Dos Santos SB, de C Guerra RM, Feitosa ML, Whaubtyfran CT, Santos-Ribeiro A: Use of neem extract in the control of acariasis by Myobia musculi Schranck (Acari: Miobidae) and Myocoptes musculinus Koch (Acari: Listrophoridae) in mice (Mus musculus var. albina L.). Neotrop Entomol. 2006, 35 (2): 269-272.
20.
go back to reference Alam A, Haldar S, Thulasiram HV, Kumar R, Goyal M, Iqbal MS, Pal C, Dey S, Bindu S, Sarkar S, Pal U, Maiti NC, Bandyopadhyay U: Novel anti-inflammatory activity of epoxyazadiradione against macrophage migration inhibitory factor: inhibition of tautomerase and proinflammatory activities of macrophage migration inhibitory factor. J Biol Chem. 2012, 287 (29): 24844-24861. 10.1074/jbc.M112.341321.PubMedCentralCrossRefPubMed Alam A, Haldar S, Thulasiram HV, Kumar R, Goyal M, Iqbal MS, Pal C, Dey S, Bindu S, Sarkar S, Pal U, Maiti NC, Bandyopadhyay U: Novel anti-inflammatory activity of epoxyazadiradione against macrophage migration inhibitory factor: inhibition of tautomerase and proinflammatory activities of macrophage migration inhibitory factor. J Biol Chem. 2012, 287 (29): 24844-24861. 10.1074/jbc.M112.341321.PubMedCentralCrossRefPubMed
21.
go back to reference Iabichella ML: The use of an extract of Hypericum perforatum and Azadirachta indica in advanced diabetic foot: an unexpected outcome. BMJ Case Rep 2013, Feb 13;2013. doi: 10.1136/bcr-2012-007299., Iabichella ML: The use of an extract of Hypericum perforatum and Azadirachta indica in advanced diabetic foot: an unexpected outcome. BMJ Case Rep 2013, Feb 13;2013. doi: 10.1136/bcr-2012-007299.,
Metadata
Title
Hypericum perforatum and neem oil for the management of acute skin toxicity in head and neck cancer patients undergoing radiation or chemo-radiation: a single-arm prospective observational study
Authors
Pierfrancesco Franco
Ilenia Potenza
Francesco Moretto
Mattia Segantin
Mario Grosso
Antonello Lombardo
Daniela Taricco
Patrizia Vallario
Andrea Riccardo Filippi
Monica Rampino
Umberto Ricardi
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2014
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-014-0297-0

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