Optimal Sequence Of Chemotherapy Research Articles

Randomized trial of postoperative adjuvant therapy in stage II and III rectal cancer to define the optimal sequence of chemotherapy and radiotherapy: A final report

4050 Background: We conducted a prospective randomized trial to define the optimal sequence of chemotherapy and radiotherapy of postoperative adjuvant treatment in stage II and III rectal cancer. Methods: Three hundred eight patients were enrolled onto the study. We randomly assigned 155 to arm I (early radiotherapy group) and 153 to arm II (late radiotherapy group). Treatment included eight cycles of chemotherapy at 4-week intervals and pelvic radiotherapy of 45 Gy in 25 fractions. Radiotherapy started on day 1 of the first chemotherapy cycle in arm I and on day 1 of the third chemotherapy cycle in arm II. The chemotherapy regimen consisted of fluorouracil 375 mg/m2/d and leucovorin 20 mg/m2/d. Chemotherapy was administered for 3 days per cycle in two cycles during the period of radiotherapy and for 5 days per cycle in the remaining six cycles. (J Clin Oncol 2002 20:1751- 8) Results: Twenty patients in arm I and 14 in arm II were not eligible. We included 274 patients in the analysis. With a median follow-up of 94 months for surviving patients, there was a trend for improved disease-free survival(DFS) in arm I compared with arm II, although it was not reached statistical significance (72% v. 63% at 7 years; P =.157). Especially, in patients who received abdominoperineal resection (APR), DFS was prolonged in arm I compared with arm II (66% v. 41% at 7 years; P=.033) Thirty six recurrences (26.7%) occurred in arm I and 49 (35.3%) in arm II (P =.151). Overall survival was not significantly different between arms I and II (71% v. 68% at 7 years; P =.855). Conclusions: With a long-term follow-up, this study failed to show a significant survival advantage for early radiotherapy with concurrent chemotherapy after resection of stage II and III rectal cancer. In patients with APR, significant improvement in DFS for arm I was observed. No significant financial relationships to disclose.

Feasibility of concurrent adjuvant chemotherapy and radiotherapy after breast‐conserving surgery in early breast cancer

The optimal sequence of chemotherapy (CT) and radiotherapy (RT) remains uncertain after breast-conserving surgery (BCS). The current study was performed to evaluate whether the concurrent RT with CT increases the toxicities. Two hundred and thirty-eight patients with stages I and II breast cancers were prospectively allocated to concurrent CT and RT (n = 133) and sequential CT and RT (n = 105) after BCS. In the sequential group, RT was started after the completion of three cycles of CT and additional three cycles of CT were delivered after RT. There was no significant difference in Grade 3 or 4 hematologic toxicities during CT between the two groups. Radiation related adverse effects were not different between the two groups. During the median follow-up period of 42 months (range: 16-60 months), 18 patients (13.5%) of the concurrent group had systemic recurrence of breast cancer, whereas 20 patients (19.1%) of the sequential group had systemic recurrence. Disease-free survival and local recurrence were not different between the two groups. Concurrent CT and RT were not associated with increased toxicity and showed reasonable cosmetic results. The current study indicates that concurrent RT and CT after BCS is a feasible treatment modality with an advantage of shortening the treatment time.

Optimal sequencing in the treatment of recurrent ovarian cancer

Improvements in ovarian cancer management mean that it may now be a long-term disease for which treatment must be carefully considered. Optimal sequencing of chemotherapy may help to enhance patients' benefit of therapy and minimize toxicity. The response to retreatment with platinum or a platinum/taxane combination is strongly influenced by the treatment-free interval after initial therapy with a platinum combination. Response rates to platinum retreatment in platinum-resistant patients (relapse within 6 months) are lower than those in platinum-sensitive patients (relapse after 6 months). Increasing the platinum-free interval by using non-platinum-based chemotherapy for treatment after relapse appears to increase the likelihood of response to later rechallenge with platinum. Many alternative agents have been investigated for the treatment of patients with relapsed ovarian cancer, including single-agent topotecan, which has been shown to achieve favorable responses. Topotecan may cause myelosuppression, which is noncumulative but tends to increase in direct correlation with the number of prior chemotherapy courses. Therefore, the best use of topotecan may be early in the course of salvage therapy. The hematologic toxicities associated with topotecan can also be reduced by adjusting the dose and schedule. Prolonged use of topotecan may be feasible and potentially beneficial in some patients.

Concurrent CMF and radiation therapy for early stage breast cancer: results of a pilot study

Purpose: The optimal sequencing of chemotherapy (CT) and radiotherapy (RT) for patients with early-stage breast cancer treated with breast-conserving therapy is unresolved. Given the concerns arising from delaying either CT or RT, we conducted a pilot study of a concurrent CT-RT regimen in the hope that this would reduce side effects without decreasing efficacy. Methods and Materials: From 1992–1994, 112 patients with 0–3 positive nodes received 6 monthly cycles of classic oral chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil (5-FU) (CMF). On day 15 of cycle 1, patients started tangential field RT (39.6 Gy in 22 fractions), followed by a 16 Gy boost in 8 fractions. Median follow-up time for surviving patients was 53 months. Results: Moist desquamation developed during or shortly after RT in 50% of patients, but only 5 patients required treatment breaks. Grade 4 neutropenia during RT occurred in 16 patients, but only 1 required hospitalization. One patient developed Grade 2 radiation pneumonitis. Ninety-three percent of patients received at least 85% of prescribed drug doses. Cosmetic scores of 51 evaluable patients approximately 2 years after the end of chemotherapy were 47% excellent, 43% good, and 10% fair. We have observed 4 local failures and 20 distant failures. Conclusions: This concurrent CT-RT scheme had acceptable toxicity and outcome. Further comparison of this approach allowing prompt initiation of both CT and RT to alternative sequences is warranted.

Radiation therapy and breast cancer.

Although the role of radiation therapy in the management of ductal carcinoma in situ is somewhat controversial, the benefit of radiation therapy in breast-conserving treatment of early stage invasive breast cancer is well established. Patients undergoing tumor excision with clear margins have low rates of recurrence with radiation therapy whether there is an extensive intraductal component or not. In all patients, there is a significantly higher risk of recurrence without radiation therapy. In patients receiving systemic therapy, the optimal sequence of chemotherapy and radiation therapy is still being defined; however, in patients with positive nodes and negative margins it is now clear that it is preferable to start chemotherapy first.

The effects of sequence and type of chemotherapy and radiation therapy on cosmesis and complications after breast conservation therapy

Purpose |: Chemotherapy plays an increasingly important role in the treatment of both node-negative and node-positive positive breast cancer partients, but the optimal sequencing of chemotherapy and radiation therapy is not well established. The purpose of this study is to evaluate the interaction of sequence and type of chemotherapy and hormonal therapy given with radiation therapy on the cosmetic outcome and the incidence of complications of Stage I and II breast cancer patients treated with breast-conserving therapy. Methods and Materials : The records of 1053 Stage I and II breast cancer patients treated with curative intent with breast-conserving surgery, axillary dissection, and radiation therapy between 1977–1991 were reviewed. Median follow-up after treatment was 6.7 years. Two hundred fourteen patients received chemotherapy alone, 141 patients received hormonal therapy alone, 86 patients received both, and 612 patients received no adjuvant therapy. Patients who received chemotherapy ± hormonal therapy were grouped according to sequence of chemotherapy: (a) concurrent = concurrent chemotherapy with radiation therapy followed by chemotherapy; (b) sequential = radiation followed by chemotherapy or chemotherapy followed by radiation; and (c) sandwich = chemotherapy followed by concurrent chemotherapy and radiation followed by chemotherapy. Compared to node negative patients, node-positive patients more commonly received chemotherapy (77 vs. 9%, p < 0.0001) and/or hormonal therapy (40 vs. 14%, p < 0.0001). Among patients who received chemotherapy, the majority (243 patients) received concurrent chemotherapy and radiation therapy with two cycles of cytoxan and 5-fluorouracil (5-FU) administered during radiation followed by six cycles of chemotherapy with cytoxan, 5-fluorouracil and either methotrexate(CMF) or doxorubicin(CAF). For analysis of cosmesis, patients included were relapse free with 3 years minimum follow-up. Results : The use of chemotherapy had an adverse effect on cosmetic outcome compared to no chemotherapy, which was of borderline significance at 3 years (92% excellent or good cosmetic outcome vs. 96% respectively, p = 0.057); however, cosmesis was not different at 5 years (91 vs. 93% respectively, p = 0.67). Cosmesis was not significantly different between patients treated sequentially and those treated concurrently (3 year: 87 vs. 93% respectively, p = 0.33), nor was it different between patients who received CMF vs. CAF (3 year: 92 vs. 93% respectively, p = 0.89). Hormonal therapy did not influence cosmetic outcome ( p = 0.78). The incidence of Grade 4 or 5 arm edema (≥ 2 cm difference in arm circumference) was 2% without chemotherapy vs. 8% with chemotherapy ( p = 0.00002). However, the incidence of arm edema was not affected by sequencing or type of chemotherapy (all p ≥ 0.52). Patients treated sequentially had a 10% incidence of Grade 4 to 5 arm edema vs. 7% in the patients treated concurrently ( p = 0.52). The incidence was 7 vs. 9% in patients treated with CMF vs. CAF ( p = 0.73. The incidence of clinical pneumonitis and rib fracture was not influenced by use of chemotherapy, sequence of chemotherapy or use of hormonal therapy (all p ≥ 0.06). Conclusions : Chemotherapy can be given concurrently with radiation therapy in the treatment of Stage I and II breast cancer with breast-conserving therapy without seriously compromising cosmetic outcome or incidence of complications compared to patients receiving other sequences of chemotherapy. Hormonal therapy did not affect cosmesis or complications. The chemotherapeutic regimen of cytoxan and 5-FU concurrent with radiation therapy followed by more chemotherapy is one reasonable option for breast conservation therapy in patients requiring chemotherapy.

The Sequencing of Chemotherapy and Radiation Therapy after Conservative Surgery for Early-Stage Breast Cancer

Patients with early-stage breast cancer who are at substantial risk for systemic metastases are increasingly treated with breast-conserving therapy and adjuvant chemotherapy. However, the optimal sequencing of chemotherapy and radiation therapy is not clear. Two hundred forty-four patients with stage I or II breast cancer who were at substantial risk for distant metastases were randomly assigned to receive a 12-week course of chemotherapy either before or after radiation therapy. All had had breast-conserving surgery. The median length of follow-up in surviving patients was 58 months (range, 10 to 124). The five-year actuarial rates of cancer recurrence at any site and of distant metastases in the radiotherapy-first group and the chemotherapy-first group were 38 percent and 31 percent (P = 0.17) and 36 percent and 25 percent (P = 0.05), respectively. Overall survival was 73 percent and 81 percent (P = 0.11), respectively. The five-year crude rates of first recurrence according to site in the radiotherapy-first and chemotherapy-first groups, respectively, were 5 percent and 14 percent for local recurrence and 32 percent and 20 percent for distant or regional recurrence or both. This difference in the pattern of recurrence was of borderline statistical significance (P = 0.07). This study suggests that for patients ar substantial risk for systemic metastases, it is preferable to give a 12-week course of chemotherapy followed by radiation therapy, rather than radiation therapy followed by chemotherapy.