Role Of Induction Chemotherapy Research Articles

The role of induction chemotherapy before radiation therapy in non-operative management of Stage III NSCLC

Radiation therapy alone has been ‘standard’ management of patients with Stage III non-small cell lung cancer for several decades. Palliative benefits are routinely achieved but significant survival benefits have not been documented. Patterns of failure in Stage III patients emphasize the need to pursue better treatment for both local macroscopic disease and distant micrometastatic sites. Improved control in both areas will be necessary to meaningfully enhance outcome for the universe of Stage III NSCLC patients. Several randomized trials show a significant survival benefit when cisplatin-containing induction chemotherapy is administered prior to locoregional treatment. In the favorable subset of Stage III patients selected for study by CALGB, the surviving fraction at 2–5 years post-therapy was ≥ 2-fold larger in the chemoradiation group than in the cohort treated with radiation alone. The French trial documented a significant decrease in distant metastases rate among the chemotherapy treated patients. In all the trials where patterns of failure are discussed, local disease persistence is the overwhelming rule. Future trials must evaluate improved induction chemotherapy approaches. Stage III patients are an ethical population in which to test induction therapy with new drug combinations randomized against already ‘active’ regimens for comparative efficacy. End points would be initial response rates, patterns of failure, and overall survival. The feasibility of high-dose chemotherapy regimens with growth factor and hematopoietic support followed by aggressive radiation must be tested. If feasible, trials randomizing high dose versus conventional dose induction programs within the context of sequential multimodality therapy should follow. Intensified radiation approaches such as hyperfractionation or CHART should be paired with active concurrent chemotherapy following induction chemotherapy alone. Pursuit of these approaches over the next several years will hopefully produce major improvements in treatment efficacy and lead to enhanced survival expectations for the large group of patients worldwide with Stage III NSCLC.

Induction chemotherapy with MVP (mitomycin-C + vindesine + cisplatin) for stage III (T1-3, N2, M0) unresectable non-small cell lung cancer: the Toronto experience

The 5-year survival rates for patients undergoing a potentially curative surgical resection for pre-operatively identified stage 3A N2 non-small cell lung cancer (NSCLC) vary from 2–13%. In an attempt to improve the curative potential of surgery, 39 patients with mediastinoscopy stage 3A unresectable N2 NSCLC received induction chemotherapy with 2 cycles of mitomycin-C, vindesine and cisplatin (MVP). Responding patients underwent thoracotomy for resection and 2 further courses of MVP. The overall response rate was 64% ( 25 39 ) with 3 complete and 22 partial responses. 22 patients were resected which included a radical mediastinal node dissection. 18 resections were complete and 4 were incomplete. Pathologically 3 patients (7.7%) had no tumor remaining. There were 2 post-op deaths secondary to a BP fistula. In addition to GI and neurologic side effects, toxicity of chemotherapy included mitomycin pulmonary toxicity in 2 patients and 4 septic deaths. 28 patients have died, 20 with recurrent or progressive disease. Of the 18 patients completely resected, 8 have recurred with a median time to recurrence of 20.6 months. Sites of recurrence include 2 loco-regional, 5 distant (2 in brain) and 1 both. Median survival of the entire 39 patients is 18.6 months with a 3-year survival of 26%. The median survival for those patients completely resected is 29.7 months with a 3-year survival of 40%. These findings suggest that MVP is an effective but toxic chemotherapeutic regimen for limited NSCLC, and although the median survival appears to be prolonged, the role of induction chemotherapy followed by surgery in stage IIIA N2 NSCLC requires a Phase III randomized trial comparing it to other treatment modalities.

Role of induction chemotherapy in invasive cervical cancer

The 386 cases of invasive cervical carcinoma treated with radiotherapy atone were statistically analyzed to delineate the high risk factors (HRFs) associated with a significantly high treatment failure rate; they were (1) stages III–IV, (2) lesion ≥4.0 cm, (3) small cell carcinoma or adenocarcinoma, (4) stages I–II with lesion ≥4.0 cm, and (5) lymphographic evidence of nodal metastasis. Then, chemoradiotherapy (induction chemotherapy plus subsequent radiotherapy) was instituted to 113 invasive cervical carcinoma patients with at least one such HRF. Each patient received two to three cycles of induction chemotherapy at about 3-week intervals. For squamous cell carcinoma, cisplatin, 100 mg/m 2 iv, was followed immediately by 5-fluorouracil, 1000 mg/m 2, as a 24-hr iv infusion × 5 days. For adenocarcinoma, cisplatin, 70 mg/m 2 iv, on Day 1 was followed by cytoxan, 250 mg/m 2, on Day 2, and adriamycin, 45 mg/m 2, on Day 3. Five-year survival of these patients according to each HRF, in the above order, was 69.1, 67.2, 68.1, 78.3, and 79.5% after chemoradiotherapy, all significantly higher than 57.4, 53.0, 54.5, 48.0, and 48.8% by radiotherapy alone. Drug toxicities such as leukopenia, hepatotoxicity, nephrotoxicity, and hypomagnesemia were seen in 46.5, 53.2, 47.1, and 55.4 % of all cycles, respectively. The toxicities altered drug schedule in 191 (61.2%) ongoing induction chemotherapy cycles. Our cisplatin-based induction chemotherapy is considered an effective preradiotherapy adjunct that can reduce treatment failure in HRF-associated invasive cervical Carcinoma.

Regional control after induction chemotherapy for adbanced squamous cell carcinoma of the head and neck: A retrospective analysis of 303 patients

Induction chemotherapy for squamous cell carcinomas of the head and neck has been the subject of a number of clinical trials with ambiguous results. Response data from phase II studies suggest a 20–40% complete response rate which has lead to an association between chemotherapy and survival and an improvement in survival when compared to historical controls. Eight separate prospective randomized trials have been published to date. Although these have yet to show an improvement in survival, there are critical flaws in each, which limit their interpretation and leave the role of induction chemotherapy an open question [1].

Role of induction chemotherapy in cervical cancer (CC)

Role of induction chemotherapy in cervical cancer (CC)

The role of induction chemotherapy in inoperable ovarian cancer.

Thirty patients with bulky advanced ovarian cancer surgically not resectable, received combination chemotherapy (median of 4.1 cycles; range, 3-7) including cisplatin or carboplatin, followed by a second surgical effort. Clinical CR + PR was observed in 24/30 (80%) patients after chemotherapy. Our study deals only with these 24 patients, and the 6 patients who did not respond to chemotherapy are not part of this report. At debulking, 7/24 (29.1%) patients had a complete macroscopic resection; 9/24 (37.5%) patients had a partial resection (residual tumor less than 2 cm). These data suggest that debulking is feasible and successful after chemotherapy containing cisplatin or its derivative. Overall median survival from diagnosis was 18.9 months; the 3-year survival rate was 28%. Median progression-free survival from diagnosis was 13.5 months. The results observed in our study indicate that the use of induction chemotherapy can play an important role in increasing the chances of optimal debulking in patients presenting with unresectable ovarian cancer.

Prognostic Variables in Head and Neck Cancer: Tumor Site, Stage, Nodal Status, Differentiation, and Immune Status

Currently the best prognostic indicator of cancer response is that of staging by the American Joint Commission Staging System. This system is most helpful in state I and in stage IV patients as a prognosticator. Caution must be exercised in oral cavity stage I cancers which tend to be more threatening and where further staging techniques should be used. The major need for careful prognostic indicators beyond simple staging is clearly evident in the stage II and stage III group. In this group, the histologic criteria of Jakobsson, the nuclear criteria suggested by Holm, and the immunologic staging parameters discussed here will hopefully better predict survival, and more importantly, guide therapy. Finally, the role of induction chemotherapy as a prognostic indicator itself has great potential and is currently being heavily investigated.