Metronomic cyclophosphamide‑induced long‑term remission after recurrent high‑grade serous ovarian cancer: A case study

Abstract

Abstract. Metronomic oral cyclophosphamide has gained increasing interest in recent years as a promising maintenance therapy in advanced, platinum-sensitive, high-grade serous ovarian cancer (HGSOC). Metronomic treatment with cyclophosphamide refers to the frequent, usually daily, administration of a low (oral) dose of cyclophosphamide with no prolonged drug-free breaks. Main advantages of this treatment are the effective reduction of tumour activity, oral administration in an outpatient setting, low cost and the low toxicity profile. Metronomic oral cyclophosphamide can benefit patients suffering from types of cancer known to be sensitive to alkylating agents, such as platinum-sensitive HGSOC. In recent years, several publications have underlined the advantage of this regimen and possible explanations were explored. We here present a patient with multiple recurrences of metastasized HGSOC, platinum-sensitive, with an on-going complete response to monotherapy with oral cyclophosphamide. This observation supports that patients with relapsing HGSOC who responded to platinum-based chemotherapy and cannot continue platinum-based chemotherapy because of toxicity, can be offered a course of metronomic cyclophosphamide. This case may serve as a reminder that old drugs can be used successfully even in the age of new upcoming therapy such as anti-angiogenic agents (VEGF inhibitors) and poly-ADP-ribose polymerase (PARP) inhibitors.

Induced Vascular Normalization—Can One Force Tumors to Surrender to a Better Microenvironment?

“…Unlike NSCLC, however, the plasma VEGF level could not be correlated to outcomes. In patients with high-grade serous ovarian cancer, metronomic CTX successfully induced long-term remission, which was thought to be largely attributable to the inhibition of ECs [ 165 ]. For patients with ovarian cancer, MC is most often used to prevent disease progression, and the effects are best achieved with another anti-angiogenic therapy [ 166 ].…”

Immunology and Immune Checkpoint Inhibition in Ovarian Cancer – Current Aspects

“…Basically, there are two approaches to prevent T reg -mediated immune escape, and thus possibly also to improve the effect of immune checkpoint inhibition: depletion of regulatory T cells or their reprogramming to IFN-γ producing, so-called Th1 T regs 49 , 66 , 67 , 68 . One possibility for selective T reg depletion is the administration of low-dose cyclophosphamide (< 250 mg/m 2 ) 69 , 70 , 71 . However, depletion does not appear to be very promising since the T regs quickly return and other T effector populations are usually suppressed as well 49 .…”

“…Th1 T regs 49 , 66 , 67 , 68 . Eine Möglichkeit der selektiven T reg -Depletion ist die Gabe von niedrig dosiertem Cyclophosphamid (< 250 mg/m 2 ) 69 , 70 , 71 . Allerdings scheint die reine Depletion letztlich wenig erfolgversprechend, da die T regs schnell wiederkommen bzw.…”

Cancer survivorship issues with radiation and hemorrhagic cystitis in gynecological malignancies

“…However, these cytotoxic agents are being tested in patients who have an intolerance for taxane or platinum based chemotherapies [5]. In one case report, low-dose metronomic cyclophosphamide treatment was described to have no urological side effects in a patient with recurrent high-grade serous ovarian cancer [6]. …”