Compared with healthy cells, glucose metabolism is greatly modified in cancer cells because
of their highly proliferative character. This differential tumor / healthy tissue property is
an opportunity to be able to propose a treatment whose therapeutic gain can be major
(targeted treatment). Preclinical studies are multiple and showed that the targeting of
overexpressed proteins (carbonic anhydrases) and involved in glycolytic metabolism can lead
to a significant anti-tumor effect. This has never been tested in humans.
Acetazolamide is a molecule commonly used for non carcinologic purposes but has demonstrated
anti-tumor activity in preclinical studies; there is also synergy radiotherapy / targeting of
carbonic anhydrases. Therefore, the investigators propose to study the combination of
acetazolamide / radiotherapy / chemotherapy with platinum and etoposide in localized Small
Cell Lung cancer.
This would be the first study:
- targeting glucose metabolism,
- testing the effectiveness of acetazolamide in oncology,
- testing the synergy radiotherapy / targeting glycolytic metabolism,
- trying to manipulate the anti-tumor immune system indirectly, by decreasing
extracellular acidosis.
Inclusion Criteria:
- Age > or = 18 years,
- Performance Status 0 to 2,
- Patient with an histologically non-metastatic localized Small cell lung cancer,
- Patient who must start radiotherapy treatment combined with chemotherapy with platinum
and etoposide, Note: The decision of the Multidisciplinary Consultation Team must be
notified in the patient's medical file,
- Evaluation lesion according to the criteria RECIST 1.1 and / or according to the
criteria PERCIST 1.0,
- Women of childbearing potential must have a negative serum pregnancy test within 72
hours of the first administration of the study treatment,
- If the patient is a woman of childbearing potential, she must be surgically sterile or
agree to use two adequate methods of contraception throughout the duration of the
study until 1 month after the last administration of the study treatment. Subjects of
childbearing potential are those who have not been surgically sterilized or have not
been free from menses for > 1 year, Note: Abstinence is acceptable if it is the
patient's usual and preferred form of contraception,
- If the male patient has one or more female partners of childbearing age, he / she must
agree to use an adequate method of contraception, starting at the first administration
of the study treatment up to 1 month after the last administration of the treatment.
of the study, Note: Abstinence is acceptable if it is the patient's usual and
preferred form of contraception,
- Patient willing and able to provide written informed consent/assent for the trial,
- Patient affiliated with a health insurance system.
Exclusion Criteria:
- Patient with metastatic disease,
- History of thoracic irradiation or near / in the thoracic irradiation field,
- Patient who refuses to participate in the study or unable to agree,
- Contraindication to thoracic radiotherapy treatment: congestive heart failure
unbalanced (ejection fraction <30%, clinical signs), severe respiratory failure:
- COPD grade IV according to the GOLD classification,
- Some GOLD III COPD and any patient with a respiratory defect defined as: oxygen
dependence and / or FEV1 <40% normal and / or, DLCO <40% predictive value and /
or vital capacity <40% predictive value,
- Contraindication to acetazolamide: hypersensitivity to acetazolamide, severe hepatic,
renal or adrenal insufficiency, sulfonamide intolerance, history of renal colic,
allergy to wheat other than celiac disease,
- Patient currently receiving one or more treatments described in section 6.9 of the
protocol,
- History of cancer, with the exception of cancers in complete remission for more than 5
years, completely resected basal cell carcinoma of the skin or squamous cell carcinoma
of the skin that has undergone potentially curative therapy or in situ cervical
cancer,
- People particularly vulnerable as defined in Articles L.1121-5 to -8 of the French
Healthcare Code, including: person deprived of freedom by an administrative or
judicial decision, adult being the object of a legal protection measure or outside a
state to express their consent, pregnant or breastfeeding women
