Mutation analysis of the BRCA1 gene in Japanese patients with sporadic ovarian cancer

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.

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A phase I study of combined trabectedin and pegylated liposomal doxorubicin therapy for advanced relapsed ovarian cancer

International Journal of Clinical Oncology ◽

10.1007/s10147-021-01973-1 ◽

2021 ◽

Author(s):

Shunji Takahashi ◽

Munetaka Takekuma ◽

Kenji Tamura ◽

Kazuhiro Takehara ◽

Hiroyuki Nomura ◽

...

Keyword(s):

Ovarian Cancer ◽

Phase I ◽

Liposomal Doxorubicin ◽

Advanced Ovarian Cancer ◽

Pegylated Liposomal Doxorubicin ◽

Japanese Patients ◽

Pharmacokinetic Analysis ◽

Dependent Manner ◽

Drug Concentrations ◽

Grade 3

Abstract Background Advanced relapsed ovarian cancer has a poor prognosis, and treatment options are limited. Methods This phase I trial investigated the dosage, safety, pharmacokinetics and efficacy of trabectedin plus pegylated liposomal doxorubicin (PLD) in Japanese patients with advanced relapsed ovarian, fallopian tube, or primary peritoneal cancer. Patients received trabectedin 0.9 or 1.1 mg/m2 immediately after PLD 30 mg/m2; both drugs were given by intravenous infusion. Treatment was repeated every 21 days until disease progression or unacceptable toxicity. The maximum tolerated dose (MTD) was determined in an initial dose escalation phase, and this was used in a subsequent safety assessment phase. Safety and tumor response were monitored throughout the trial, and drug concentrations for pharmacokinetic analysis were measured during cycle 1. Results Eighteen patients were included. The MTD of trabectedin was determined as 1.1 mg/m2. Gastrointestinal adverse events were experienced by all patients, but were mostly grade 1 or 2 in intensity. Most patients had grade ≥ 3 elevations in transaminase levels or grade ≥ 3 reductions in neutrophil count, but these events were generally manageable through dose reduction and/or supportive therapies, as appropriate. There were no deaths during the trial. Trabectedin exposure increased in a dose-dependent manner. The overall response rate was 27.8%. Conclusions Trabectedin, in combination with PLD, may have clinical benefits in Japanese patients with relapsed advanced ovarian cancer. The recommended dosage of trabectedin for further study in this population is 1.1 mg/m2 once every 21 days. Clinical trial registration number: JapicCTI-163164

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Long-Term Follow-Up of a Female Patient Treated with Olaparib—Hope for a Long Life without Relapse?

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18073430 ◽

2021 ◽

Vol 18 (7) ◽

pp. 3430

Author(s):

Mateusz Kozłowski ◽

Katarzyna Nowak ◽

Aneta Cymbaluk-Płoska

Keyword(s):

Ovarian Cancer ◽

Parp Inhibitor ◽

Brca1 Gene ◽

High Specificity ◽

Reproductive Organs ◽

Platinum Based Chemotherapy ◽

Long Term Follow Up ◽

History Of ◽

Advanced Stages

Ovarian cancer is one of the most common cancers of the reproductive organs. As there are no symptoms in the early stages, it is mainly detected in the advanced stages. Even then, the symptoms are non-specific and include, for example, abdominal pain, early satiety, or changes in bowel habits. Both biochemical marker levels and imaging studies are used in the initial diagnosis. However, it should be emphasized that they are not characterized by high specificity. Treatment is multistage, and usually first-line debulking surgery is used followed by platinum-based chemotherapy. Here we present a clinical case of a 56-year-old female, a carrier of a mutation in the BRCA1 gene, with a history of breast cancer and with recurrent epithelial ovarian cancer. The patient was qualified for treatment with a PARP inhibitor and is currently undergoing treatment with olaparib. In the patient’s follow up of 50 months to date, there has been no recurrence of cancer. Few side effects have been observed, and the most serious one that can be effectively treated is anemia. On the basis of the described case, the authors concluded that olaparib treatment is effective, relatively safe, and does not significantly affect daily functioning.

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