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R Pazdur

Publications and source records attributed to R Pazdur.

At least 91 records · Page 5Linked to original sources
PubMed1995

Docetaxel.

PURPOSE: We reviewed the preclinical and clinical profiles of the antineoplastic taxoid docetaxel (Taxotere, Rhône-Poulenc Rorer, Collegeville, PA). DESIGN: From the literature and manufacturer's data, we detail docetaxel's activity, tolerability, and pharmacokinetics in preclinical and phase I studies and its activity and side effects in phase II trials in various neoplasms. RESULTS: Docetaxel promotes the assembly of and stabilizes microtubules, preventing their depolymerization. In phase I studies in patients with solid tumors refractory to standard chemotherapy, docetaxel's major dose-limiting toxicity (DLT) was dose- but not schedule-dependent neutropenia; another major side effect was schedule-dependent grade 3 mucositis. Other, generally less severe effects included hypersensitivity reactions (HSRs), neurotoxicities, cutaneous reactions, alopecia, and asthenia. Responses were observed in breast, bronchial, and ovarian carcinomas. The recommended dose for phase II studies was 100 mg/m2 as a 1-hour intravenous (i.v.) infusion every 3 weeks. Preliminary phase II results confirmed docetaxel's activity against breast, non-small-cell and small-cell lung, ovarian, head and neck, and gastric cancers; melanoma; and soft tissue sarcomas. Neutropenia again was the principal dose-limiting side effect. Nonhematologic effects, usually grade 1 or 2, including HSRs, were common. HSRs were manageable with premedication. Corticosteroid premedication partially alleviated fluid retention seen after repeated docetaxel courses. Studies are evaluating docetaxel in various combination regimens in advanced breast cancer, non-small-cell lung cancer, and other solid tumors. CONCLUSION: Multicenter and single-institution studies have demonstrated docetaxel's consistent significant activity in various cancers. Phase III and combination therapy trials are ongoing. Work is in progress to understand and prevent/resolve some of this drug's side effects.

Adult↗
PubMed1995

Controlled clinical trial of interferon-gamma as postoperative surgical adjuvant therapy for colon cancer.

PURPOSE: The primary goal of this study was to assess the effectiveness of interferon gamma (IFN-gamma) to prevent tumor relapse following potentially curative surgery in patients with high-risk colon cancer. A secondary goal was to determine the effect of IFN-gamma on immune function and to correlate alterations in immune parameters with survival. PATIENTS AND METHODS: Three to 4 weeks after undergoing resection of all known malignant disease, 99 patients with stage II, III, or IV colon cancer were randomly assigned to receive IFN-gamma 0.2 mg total dose by subcutaneous injection daily for 6 months or observation. Serial assessment of human leukocyte antigen (HLA)-DR expression and Fc receptors on peripheral-blood monocytes was conducted in 24 patients who received IFN-gamma and 27 control patients. RESULTS: With a median follow-up duration of 59 months in patients still alive, there was evidence of a detrimental effect on time to relapse (P = .03) among patients who received IFN-gamma. There was no significant difference in patient survival (P = .12). This study has sufficient power to rule out a 25% reduction in death rate for patients who received IFN-gamma (P < .05). Significant enhancement of immune function was observed in patients treated with IFN-gamma as measured by HLA-DR expression (P < .01) and Fc receptors (P < .001) on peripheral-blood monocytes. CONCLUSION: This study effectively rules out any clinically meaningful benefit for IFN-gamma as surgical adjuvant treatment for patients with high-risk colon cancer. Although significant enhancement of nonspecific immune function was seen with this dosage administration schedule of IFN-gamma, this was not associated with any demonstrable antitumor effect.

Adult↗
PubMed1994

Activity of taxol in patients with squamous cell carcinoma and adenocarcinoma of the esophagus.

BACKGROUND: Carcinomas of the esophagus and gastroesophageal junction are uncommon and account for approximately 1% of all malignancies in the United States. Advanced squamous cell carcinoma or adenocarcinoma of these sites remains incurable. The median survival of patients is between 4 and 8 months, and their prognosis has not changed in the past several decades. Undoubtedly, there is an urgent need to develop new effective drugs for patients with carcinoma of the esophagus or the gastroesophageal junction. PURPOSE: Our purpose was to evaluate the response rate, duration of response, and toxic effects in previously untreated patients with unresectable local-regional or metastatic carcinoma of the esophagus who were enrolled in a phase II study of paclitaxel (Taxol). METHODS: Fifty-two patients with either metastatic or local-regional unresectable carcinoma of the esophagus were eligible for this study. All patients were premedicated with dexamethasone, cimetidine, and diphenhydramine hydrochloride to prevent allergic reaction. The starting dose of paclitaxel was 250 mg/m2 repeated every 21 days. Patients received 5 micrograms/kg granulocyte-colony stimulating factor (G-CSF) subcutaneously daily 24 hours after the completion of paclitaxel to reduce the duration and severity of granulocytopenia. RESULTS: Of the 52 patients who were initially enrolled, 50 (44 men and six women) were evaluated for toxic effects and response. Thirty-two had adenocarcinoma, and 18 had squamous cell carcinoma. The median age was 58 years (range, 36-77 years). The median Zubrod performance status was 1 (range, 0-1). The median number of courses was four, and the total number of courses administered was 227. The median dose of paclitaxel was 250 mg/m2 (range, 150-280 mg/m2). Paclitaxel dosage was reduced in 52 (23%) of 227 courses and increased in 15 (7%) of 227 courses. Sixteen (32%) patients achieved either a complete or partial response, and 11 (22%) achieved a minor response. Among 32 patients with adenocarcinoma, 11 (34%; 95% confidence interval [CI] = 18%-50%) had either a complete or partial response and six had a minor response. Five (28%; 95% CI = 7%-49%) of 18 patients with squamous cell carcinoma had a partial response, and five (28%) had a minor response. The median duration of partial response was 17 weeks (range, 7 to > or = 58 weeks). At a median follow-up of 9 months, 32 patients remain alive, with an actuarial median survival duration of 13.2 months (range, 2 to > or = 17.5 months). Paclitaxel followed by G-CSF was very well tolerated. CONCLUSIONS: These data indicate that paclitaxel is an active agent against adenocarcinoma and squamous cell carcinoma of the esophagus.

Adenocarcinoma↗
PubMed1994

Medical management of colorectal carcinomas.

Current information on the medical treatment of colorectal cancer was reviewed after a search of the literature through Medline. Publications from 1984 to present were surveyed. Appropriate adjuvant therapy increases overall survival and disease-free intervals. The treatment modalities of unresectable or metastatic tumors are disappointing, with at best 40% of patients experiencing short-lasting responses. Whenever possible, patients with advanced colorectal cancer should be enrolled in clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Phase II trial of piroxantrone in metastatic gastric adenocarcinoma.

Piroxantrone, a synthetic intercalating agent, was studied in patients with advanced, measurable gastric adenocarcinoma who had not received prior chemotherapy. The starting piroxantrone dose was 150 mg/m2 given intravenously over 1 hour on day 1 and repeated every 21 days. Response and toxicity could be evaluated in 15 patients. No complete, partial, or minor responses were observed. Toxic effects included granulocytopenia, anemia, vomiting, nausea, anorexia, fatigue, stomatitis, alopecia, hyperbilirubinemia, and increased alkaline phosphatase levels. At the stated dose and schedule, piroxantrone does not possess significant activity against advanced gastric cancer.

Adenocarcinoma↗
PubMed1994

Phase II trial of intravenous melphalan in advanced colorectal carcinoma.

BACKGROUND: Relatively few studies have examined the activity of alkylating agents in the treatment of advanced colorectal adenocarcinoma. Recent reports have suggested possible therapeutic activity for high-dose intravenous melphalan administered with autologous bone marrow transplantation (BMT) support. We conducted a phase II study to determine the efficacy of administering intravenous melphalan at doses that do not require BMT support in patients with advanced colorectal adenocarcinoma. PATIENTS AND METHODS: Fifteen patients with histologically proven, bidimensionally measurable disease were treated. The starting dose of melphalan was 30 mg/m2, with dose escalation permitted. RESULTS: No objective responses were observed. Toxic effects were primarily reversible granulocytopenia and thrombocytopenia. There were no treatment-associated deaths. CONCLUSION: Melphalan's lack of efficacy at the doses administered does not disprove the steep chemotherapy dose-response relationship postulated for many solid tumors. However, we feel that it is unlikely that repetitive courses of high dose melphalan with autologous BMT support will be a practical approach to the management of advanced colorectal adenocarcinoma.

Adenocarcinoma↗
PubMed1994

Phase II trial of edatrexate in patients with advanced pancreatic adenocarcinoma.

BACKGROUND: The methotrexate analogue 10-ethyl-10-deazaaminopterin (10-EdAM, or edatrexate) has shown antitumor activity in preclinical testing and clinical studies of patients with breast, lung and head and neck carcinomas. A phase II study was conducted in patients with advanced pancreatic adenocarcinoma. PATIENTS AND METHODS: Forty patients were enrolled on the clinical trial. Edatrexate was administered intravenously at a dose of 80 mg/m2 weekly for 5 weeks. The treatment course was repeated every 6 weeks. RESULTS: Two partial responses were observed. Both of these patients had partial responses which lasted 2 and 3.5 months. The median survival for all patients was 3.5 months. Serious (grade 3 or 4) toxic effects were primarily mucosal, hematologic, and dermatologic. Two patients experienced severe pulmonary toxic reactions. CONCLUSION: At the dose and schedule used, edatrexate was poorly tolerated and did not demonstrate significant antitumor activity.

Adenocarcinoma↗
PubMed1994

Phase II trial of docetaxel (Taxotere) in metastatic colorectal carcinoma.

BACKGROUND: Docetaxel (Taxotere) is prepared from a noncytotoxic precursor extracted from the needles of the Taxus baccata. Preclinical investigations have demonstrated that docetaxel is very active in colon adenocarcinoma murine models. Phase I studies revealed granulocytopenia to be the dose-limiting toxicity. Initial clinical trials also demonstrated docetaxel's activity in ovarian, breast, and non-small cell lung cancer. Because of this encouraging preclinical and clinical activity, we initiated a phase II study of docetaxel in patients with metastatic colorectal carcinoma. PATIENTS AND METHODS: Docetaxel, 100 mg/m2, was administered as a 1-hour intravenous infusion every 21 days. Nineteen patients were entered on the trial. All patients had measurable disease and had not received prior chemotherapy for metastatic disease. RESULTS: No complete or partial responses were observed. Granulocytopenia was the dose-limiting toxic effect. Seventeen patients had grade 4 granulocytopenia; 8 of these patients received antibiotics for neutropenic fevers. Twelve patients experienced hypersensitivity reactions, and 15 patients experienced cutaneous toxic reactions. One patient demonstrated evidence of fluid retention. CONCLUSIONS: Administered at the stated dose and schedule, docetaxel has little activity against metastatic colorectal carcinomas. The toxicity profile, consisting of granulocytopenia, hypersensitivity reactions, cutaneous reactions, and edema, has been previously described in patients receiving docetaxel.

Adenocarcinoma↗
PubMed1994

Phase II trial of edatrexate in patients with advanced hepatocellular carcinoma.

BACKGROUND: The methotrexate analogue edatrexate (10-ethyl-10-deaza-aminopterin, or 10-EDAM) has demonstrated greater activity than methotrexate has against murine tumors and human tumor xenografts. Phase II trials of edatrexate have already demonstrated its activity against breast, lung, and head and neck carcinomas. A phase II trial of edatrexate was conducted in patients with advanced hepatocellular carcinoma. PATIENTS AND METHODS: Seventeen patients with previously untreated unresectable hepatocellular carcinoma were enrolled on the study. Edatrexate, 80 mg/m2 weekly for 5 weeks, was administered intravenously. The treatment course was repeated every 6 weeks. Tumor response was evaluated by computerized tomographic scan after 2 courses. RESULTS: No complete or partial responses were observed in this trial. Two minor responses, each lasting less than 12 weeks, were observed. Twelve patients had elevated serum alpha-fetoprotein (AFP) levels at entry into the study; 4 of the 12 patients experienced a > or = 25% decrease in the level of this tumor marker; 3 of the 4 had a > 50% reduction in AFP level. Grade 3 and 4 toxic effects were granulocytopenia, thrombocytopenia, anemia, oral mucositis, skin reactions, fatigue, anorexia, and diarrhea. CONCLUSIONS: Edatrexate administered at this dose and schedule appears to have little therapeutic efficacy against advanced hepatocellular carcinoma.

Adult↗
PubMed1994

Phase II trial of uracil and tegafur plus oral leucovorin: an effective oral regimen in the treatment of metastatic colorectal carcinoma.

PURPOSE: To determine the activity and evaluate the toxicity of uracil and tegafur in a 4:1 molar concentration (UFT; Taiho Pharmaceutical Ltd, Tokyo, Japan) plus oral calcium leucovorin in the treatment of patients with advanced colorectal carcinoma. PATIENTS AND METHODS: Forty-five patients with advanced, bidimensionally measurable metastatic colorectal carcinoma were enrolled onto the trial. None of the patients had received prior chemotherapy or biologic therapy for advanced disease. Patients received either 350 or 300 mg/m2/d UFT plus 150 mg/d leucovorin administered orally in divided daily doses every 8 hours for 28 days followed by a 7-day rest period. Response was evaluated after two courses of therapy. RESULTS: Eighteen patients (three treated at 350 mg/m2/d and 15 at 300 mg/m2/d) had partial responses, and one patient had a complete response (response rate, 42.2%; 95% confidence interval, 28% to 58%). Responses were observed in sites that included liver (n = 18), lung (n = 6), and bone (n = 1). Of seven patients who received 350 mg/m2 UFT, prolonged grade 3 diarrhea developed in five; this resulted in a reduction in the UFT starting dose to 300 mg/m2/d in the remaining 38 patients. Grade 1 or 2 toxic effects included diarrhea, nausea, vomiting, abdominal cramping, anorexia, fatigue, oral mucositis, excessive lacrimation, and rash. Among 38 patients who received the 300-mg/m2/d dose, grade 3 toxic reactions included diarrhea (n = 4), vomiting (n = 2), abdominal cramping (n = 1), and fatigue (n = 2). CONCLUSION: UFT 300 mg/m2/d plus oral leucovorin 150 mg/d administered for 28 days demonstrated significant activity against metastatic colorectal carcinoma. This oral regimen was well tolerated and devoid of the neutropenia or significant oral mucositis that complicates intravenous schedules of fluorouracil (5-FU) plus leucovorin. The results of this clinical trial will serve as the basis for a randomized phase III study to compare this oral schedule of UFT plus leucovorin with intravenous 5-FU plus leucovorin to determine the relative efficacy, impact on quality of life, and cost of the two regimens.

Administration, Oral↗
PubMed1994

A phase II trial of paclitaxel (Taxol) in advanced esophageal cancer: preliminary report.

A cooperative, phase II single-arm trial was conducted at two large tertiary referral cancer centers to evaluate the antineoplastic activity and toxicities of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of patients with advanced esophageal cancer. The drug was given at a dose of 250 mg/m2 as a 24-hour continuous infusion. Repeat courses were given at 21-day intervals. De-escalation was based primarily on myelosuppression. All patients received recombinant human granulocyte colony-stimulating factor to minimize the risk of neutropenic fever. The primary goal of the study was tumor response. In the trial, which is ongoing, 42 patients have been assessed to date. Adenocarcinoma was the predominant histology in 30 patients, while epidermoid cancer was seen in 13 patients. Paclitaxel was identified as an active agent. Thirty percent of patients with adenocarcinoma and 25% of the smaller group with epidermoid carcinoma have had partial remissions. Complete remissions have not been seen to date. The median duration of response was 9 weeks. The major toxicity was myelosuppression; 11 patients required admission for neutropenic fever on 13 different occasions. Paclitaxel is an active drug in the treatment of esophageal cancer. Currently, there does not appear to be a difference in response on the basis of histologic subtype. Further studies with paclitaxel in combination with other drugs (eg, cisplatin and 5-fluorouracil), on different treatment schedules, and as part of multimodality therapy are indicated.

Adenocarcinoma↗
PubMed1993

Low serum alpha-fetoprotein level in patients with hepatocellular carcinoma as a predictor of response to 5-FU and interferon-alpha-2b.

BACKGROUND: A Phase II clinical trial was conducted to evaluate the efficacy of intravenous fluorouracil (5-FU) and subcutaneous recombinant interferon-alpha-2b (rIFN-alpha-2b) in the treatment of hepatocellular carcinoma (HCC) and to define factors that might be predictive of a response to treatment. METHODS: Twenty-nine patients were registered on the protocol. 5-FU was administered as a continuous intravenous (i.v.) infusion (dose = 750 mg/m2) for 5 consecutive days. rIFN-alpha-2b was administered subcutaneously (SC) (dose = 5 x 10(6) um/m2) once a day on days 1, 3, and 5 of the 5-FU infusion. The treatment was repeated at 14-day intervals. Responses were assessed at the end of one course of therapy, which was equivalent to four treatments. RESULTS: Of the 28 patients evaluable for response, 5 (18%) had a partial response, and 1 (4%) had a minor response. Responses lasted from more than 2 to more than 24 months (median, 11.5 months). Ten (36%) patients experienced no response, and 12 (43%) had progressive disease. The 6 responders were part of a group of 16 patients who had pretreatment levels of serum alpha-fetoprotein (AFP) of 50 ng/ml or less and a group of 8 whose tumors involved 50% or less of the liver parenchyma. Mucositis, which occurred in 54% of the patients, was the most common toxicity associated with the treatment regimen. Diarrhea and dermatitis were observed in 16% and 17% of the patients, respectively; fatigue, thrombocytopenia, granulocytopenia, neurologic toxicity, and nausea and vomiting were not commonly seen. CONCLUSIONS: The regimen of i.v. 5-FU and SC rIFN-alpha-2b was well tolerated and induced durable partial response in 31% (5 of 16) of patients with HCC who had low levels of serum AFP and in those with 50% or less of liver replacement. In contrast, the treatment regimen was ineffective in patients with HCC who had high levels of serum AFP or extensive liver disease.

Adolescent↗
PubMed1993

Phase II evaluation of recombinant alpha-2a-interferon and continuous infusion fluorouracil in previously untreated metastatic colorectal adenocarcinoma.

BACKGROUND: Thirty-nine patients with advanced measurable metastatic colorectal carcinoma were entered in a clinical trial of recombinant alpha-2a-interferon (r alpha-2a-IFN) and continuous-infusion 5-fluorouracil (5-FU). Patients had not been treated previously with chemotherapy and had bidimensionally measurable disease. METHODS: A course of therapy consisted of a 5-day continuous infusion of 5-FU, 750 mg/m2/day, with r alpha-2a-IFN, 9 x 10(6) IU, subcutaneously, on days 1, 3 and 5 of the 5-FU infusion. A course of therapy was repeated every 15 days, and patients were examined for response after receiving four courses of therapy. RESULTS: One patient had a complete response, and 11 patients experienced partial responses, for an overall response rate of 31% (95% confidence interval [CI], 17-48%). The median duration of response was 7.5 months (range, 2-13 months). Fifty-two percent of the patients entered in this trial are alive at time of this writing, with a median follow-up duration of 12.2 months (range, 6-24 months). Grade 3-4 toxicities included mucositis (nine patients), diarrhea (two patients), granulocytopenia (two patients), and fatigue (three patients). CONCLUSION: This regimen of 5-FU with r alpha-2a-IFN administration does not appear to be superior to previously published schedules of 5-FU with r alpha-2a-IFN or to other methods that modulate 5-FU.

Abdominal Neoplasms↗
PubMed1993

Systemic therapies for unresectable primary hepatic tumors.

Clinical trials evaluating systemic therapies for hepatocellular carcinomas (HCCs) must take into consideration prognostic factors that influence survival. Clinical features such as poor performance status, older age, and the presence of jaundice may be predictive of short survivals. Because patients with elevated alpha-fetoprotein (AFP) levels have short survivals, randomized clinical trials of therapy for HCC should stratify patients based on AFP levels. Numerous clinical trials of single-agent chemotherapy for HCC have examined alkylating agents, antitumor antibiotics, anthracyclines, hormonal therapies, and interferons. However, these trials have failed to demonstrate an agent that consistently produces response rates greater than 20% or that improves survival. Similarly, effective combination chemotherapy regimens for HCC have not been identified. Clinical trials have also failed to identify effective systemic therapies for cholangiocarcinomas, although these trials have had limited numbers of patients. These dismal results mandate an examination of phase II agents in untreated good-performance patients with HCC. Novel approaches to drug delivery should also be pursued.

Antineoplastic Agents↗
PubMed1993

Pediatric hepatic tumors: clinical trials conducted in the United States.

Hepatoblastomas (HBs) and hepatocellular carcinomas (HCCs) constitute the majority of hepatic tumors in children. Although most children who have HB or HCC present with unresectable disease, chemotherapy may reduce the size of the primary tumor and metastases, thus allowing subsequent successful removal. Clinical trials conducted over the past decade in the United States have demonstrated that chemotherapy regimens consisting of continuous-infusion doxorubicin and cisplatin or high-dose cisplatin alone effectively reduce tumor size. The prognosis of children with HB is better than that of those with HCC. Over half the patients who initially have unresectable HB can be rendered disease free with chemotherapy and subsequent surgery.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

The taxoids: paclitaxel (Taxol) and docetaxel (Taxotere).

The taxoids, paclitaxel (Taxol) and docetaxel (Taxotere), represent a novel class of antineoplastic drugs. Paclitaxel and docetaxel share a similar mechanism of action: the promotion of microtubule assembly and inhibition of microtubule disassembly. The clinical development of paclitaxel was initially hampered by hypersensitivity reactions (HSRs). The use of premedications and prolongation of the infusion time to 24h has reduced these reactions and allowed this drug's clinical development. Although paclitaxel's clinical activity has not been fully investigated, clinical trials have demonstrated its activity against ovarian, breast, and bronchial carcinomas. Because phase I studies of docetaxel noted occasional HSRs and these observations increased with further clinical experiences, those premedications employed with paclitaxel have now been instituted in many phase II studies of docetaxel. Docetaxel is currently being investigated in ovarian, breast, and bronchial carcinomas and has shown impressive clinical activity. The dose-limiting toxicity of both these agents is neutropenia; myalgias, mucositis, neuropathies, and alopecia have also been observed with both drugs. Additionally, a fluid retention syndrome and cutaneous toxicities have been noted in patients treated with docetaxel. Future studies of the taxoids will allow further comparisons of the toxicity and efficacy of these agents.

Animals↗
PubMed1993

Intensive preoperative chemotherapy with colony-stimulating factor for resectable adenocarcinoma of the esophagus or gastroesophageal junction.

PURPOSE: The curative resection rate in patients with potentially resectable carcinoma of the esophagus is approximately 55% and their median survival time is 11 months. Preoperative chemotherapy with high doses of chemotherapeutic agents was used to evaluate clinical and pathologic responses, curative resection rate, toxicity, and survival. Colony-stimulating factor (CSF) was added to reduce the severity of myelosuppression. PATIENTS AND METHODS: Twenty-six consecutive assessable patients with potentially resectable adenocarcinoma of the esophagus or gastroesophageal junction were treated with two preoperative courses of intensive chemotherapy (etoposide, doxorubicin, and cisplatin [EAP]) with granulocyte-macrophage CSF (GM-CSF). Additional three conventional-dose postoperative chemotherapy courses without GM-CSF were given to patients who responded to preoperative chemotherapy. RESULTS: A median of three courses (range, one to six), were administered. Of 27 patients, 26 were assessable for response to preoperative EAP; 13 (50%) achieved a major response. Among 23 patients who underwent surgery, 15 (65%) had a curative resection (58% of 26 assessable patients); none of the patients had a pathologic complete response, but two patients had only microscopic carcinoma in the resected specimen. Six patients had carcinoma present at the resection margins and received postoperative radiotherapy. Two patients were found to have liver metastases at exploration. At a median follow-up of 22 months, the median survival of 26 patients was 12.5 months (range, 2 to 32 +). Fourteen patients died of their carcinoma; two patients died of treatment-related causes; one died of an unrelated CNS arterial malformation; and the causes of death in two patients remain unknown. Seven patients are alive with no evidence of relapse. Major toxicities of this regimen included severe myelosuppression, nausea and vomiting, infections, and severe constitutional symptoms related to GM-CSF. However, subcutaneous injection of GM-CSF was well tolerated. CONCLUSION: High-dose EAP is active against locoregional adenocarcinoma of the esophagus and gastroesophageal junction but can be associated with significant toxicity. Although this strategy remains attractive and needs to be developed further, less toxic and more effective regimens need to be identified.

Adenocarcinoma↗