Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05410314 |
| Other study ID # |
UNIBA |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
February 7, 2020 |
| Est. completion date |
December 7, 2021 |
Study information
| Verified date |
May 2022 |
| Source |
University of Bari Aldo Moro |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The progressive improvement of lymphoma treatment has led to an important prolongation of
patient survival and life expectancy. Therefore, the principal International scientific
societies of oncology, recommend Long-term Survivors of Lymphoma to join fertility programs.
Specifically, fertile age patients should be assisted by a multi-disciplinary team including
specialists dedicated to fertility preservation in oncology, in order to support the
completion of the reproductive project. In general population, the use of Inositol was
spready considered an effectives choice to contrast ovarian dysfunction with consequently
improvement of reproductive outcomes, so it may represent an adjuvant strategy for this
purpose. Therefore, the investigators conducted a pilot study to evaluate the potentialities
of this nutritional supplement with the aim to optimize the reproductive function in
Long-term Survivors of Lymphoma. Despite the limited number of cases and short observational
time, this pilot investigation could represent a potential cornerstone for further insights,
discussions, and applications
Description:
Anticancer regimens are usually used to treat patients with lymphoproliferative neoplasms
with a consequently transitory or permanent damage to their reproductive functionalities.
Rates of gonadotoxicity of each chemotherapy could be modulated according to dose intensity,
number of courses, and type of agent or combination. Classical Hodgkin lymphoma (cHL) and
Diffuse Large B-cell lymphoma (DLBCL), including primary mediastinal Large B-cell Lymphoma
(PMBL) have usually higher incidence in the 2nd or 3rd decade of life and presents cure rates
of more than 75% 3,4 These histotypes need a poli-chemotherapy with ABVD (adriamycin,
bleomycin, vinblastine, dacarbazine), which involves the association of alkylating and
non-alkylating agents.
The autologous hemato-poietic stem cell transplant (ASCT) is needed in about the 10% of cHL
and the 40% of DLBCL and has higher impact on fertility compared to ABVD 6. Therefore, both
the chemotherapy (damaging the primordial follicle pool and then the ovarian reserve, OR) and
the radiotherapy (exclusively secondary to under diaphragmatic and pelvic irradiation) could
represent a risk of gonadotoxicity . In this scenario, data concerning fertility in cHL have
been mainly evaluated by the German Hodgkin Study Group (GHSG) and the European Organization
for Research and Treatment of Cancer (EORTC) through amenorrhea and anti-Mullerian hormone
(AMH) evaluation. Indeed, amenorrhea has been used in numerous research to assess the
gonadotoxicity of oncological treatment and reflect ovarian function . Furthermore, AMH could
represent a gonadotoxicity marker, since it decreases during chemotherapy and could improve
after the end of treatment, depending upon specific treatment schemes . Literature showed
that after early-stage disease treatment (2 -4 cycle), more than 90% of patients reported a
low gonadotoxic effect with a regular menstrual cycle after therapy (median recovery of 1
year). For advanced stage diseases (treated with 6 courses of ABVD) the gonadotoxic effect
vary on base of patient's aged. Indeed, the complete AMH restoring during the 3-years
follow-up period, was detected in all women under 35 years, and only 37% of older ones .
Moreover, in a Cochrane meta-analysis, gonadotropin-releasing hormone agonist (GnRHa)seems to
be effective in shielding the ovaries during chemotherapy, in terms of treatment-related
premature ovarian failure, ovulation and menstruation recovery.
Beyond the ovarian suppression with GnRHa, there are several well-established procedures
(oocyte cryopreservation, ovarian cortex cryopreservation for woman and sperm
cryopreservation for men) that could prevent impact of these therapies in young patients.
Therefore, considering the increased life expectation nowadays of Long-term Survivors of
Lymphoma (patients in complete remission of the disease for more than 5 years) a fertility
program with multi-disciplinary counselling is indicated. Particularly, in order to assess
the damages upcoming after anticancer therapies on reproductive organs, international
scientific societies such as the American Society for Reproductive Medicine (ASRM) (Ethics
Committee of American Society for Reproductive Medicine, 2013), the American Society of
Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO) as well as the
International Society for Fertility Preservation (ISFP), strongly recommend a personalized
and multidisciplinary counseling for each patient. In particular, the surveillance programs
for the management of long-term lymphoma survivors should involve a team with
onco-hematologists, radiotherapists, cardiologists, an endocrinologist, a psychologist,
gynecologist, urologist and a nutritional biologist. The goal is to provide individualized
therapeutic possibilities to restore endocrine function. Following these recommendations, an
ambulatorial service dedicated to fertile patients with oncological disease was instituted in
our Clinic of Gynecology Oncology, aiming to perform a careful assessment of the fertility
state and support the reproductive project of those patients.
In these women,the investigators primarily estimated AMH, Follicle stimulating hormone (FSH),
Luteinizing hormones (LH), 17β-estradiol ,in association to antral follicles count (AFC)
assessed by ultrasonography during the cycle follicular phase. During this clinical
evaluation, several patients often reported menstrual irregularities due to anovulatory
cycles (50%), dysmenorrhea (20%) and abnormal uterine bleeding (30%).
Considering these elements, one of the potential therapeutic options could be considered the
oral supplementation with Myo-Inositol and D-Chiro-Inositol (MIC). Indeed, MIC over the years
has tiptoed to come alongside the classic pharmacological therapies, with robust compliance,
safety, and effectiveness. MIC showed great potentiality to contrast ovarian dysfunction and
optimize the reproductive function.
Therefore, the investigators conducted a prospective observational controlled study, with the
aim to assess the effects of oral supplementation with MIC on ovarian function parameters in
Long-term Survivors of Lymphoma.
