Chemotherapy

Chemo Secrets From a Breast Cancer Survivor

Breast Cancer Survivors

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Numerous trials of chemotherapy, used either in an adjuvant or neo-adjuvant setting have not demonstrated benefit. Most of the earlier trials involved single or multiple agents in a phase II setting. More recent studies have involved the use of neo-adjuvant chemotherapy or concurrent chemotherapy and/or radiation sensitizers with irradiation. Although results from some of these trials were initially encouraging, the final results have been uniformly disappointing as well (44,45,47-50).

Etoposide (VP-16) was used to treat 12 patients at the time of tumor progression, and demonstrated a remarkable 50% response rate, which was durable for a median of 8 mo. The dosing of etoposide was a conventional regimen (50 mg/m2/d x 21 d with 14 d of rest between cycles). All patients had received prior radiotherapy at diagnosis (51). Subsequent studies using various agents have failed to show consistent results and to date there is no standard relapse therapy given to patients with this tumor.

The Children's Cancer Group conducted a randomized trial of two different arms of intensive pre-irradiation chemotherapy followed by hyperfactionated radiotherapy. Children were randomly assigned to receive three courses of carboplatin, etoposide, and vincristine (arm A, n = 32), or cisplatin, etoposide, cyclophosphamide, and vincristine (arm B, n = 31). Granulocyte colony-stimulating factor was used in both arms. Following chemotherapy, both groups received 7200 cGy of radiation in 100 cGy bid fractions. The radiographic response rate to the chemotherapy was 10 ± 5% in arm A and 18 ± 9% in arm B. Event-free survival was 17 ± 5% at 1 yr and 6 ± 3% at 2 yr. Although those children that responded to the chemotherapy had a longer survival, the authors concluded that neither chemotherapy regimen meaningfully improved response rate, event-free survival, or overall survival (52).

In a study using standard dose radiotherapy (54-60 Gy in 1.5-1.8 Gy/d daily fractions) and high-dose tamoxifen (200 mg/m2/d) the median survival was 10.3 mo, with a 1-yr survival rate of 37.0 ± 9.5%, which the authors conclude did not improve the prognosis for this tumor (53).

The most intensive chemotherapy regimen has employed high-dose chemotherapy with autologous bone marrow rescue, which failed to improve survival for children with this tumor (54).

Effective therapy for the intrinsic pontine glioma has remained one of the most elusive in neurooncology. Most investigators conclude that the standard approach to treating these tumors begins with staging of the tumor and if contained to the pons, treating with standard dose radiotherapy delivered in a single daily fraction to the tumor plus a 1- to 2-cm margin. Leptomeningeal dissemination is present in one-third of children at diagnosis and if identified at diagnosis, or at any time in the illness, radiotherapy can be used with a palliative attempt to treat the involved areas. Although there is no evidence that neoadjunctive or adjunctive chemotherapy prolongs the time to relapse, the use of low-dose etoposide or experimental agents may be considered at relapse. The survival in patients with this particular tumor has not improved in the last several decades despite escalating both radiation and cytotoxic chemotherapy dosing to the maximum tolerated levels. Further advances will likely require a unique chemotherapeutic agent or biological agent.

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