Chemotherapy regimens in rare solid tumors E-Book

Alessandro Comandone

• Herausgeber: SEEd Edizioni Scientifiche
• Kategorie: Fachliteratur
• Sprache: Englisch

Veröffentlichungsjahr: 2011

Beschreibung

Rare tumors (RT) are an increasing problem in oncology. The main characteristic of RT is the low frequency of the event, that determines difficult and sometimes late diagnosis and a great uncertainty in diagnosis and treatment. The aim of this book is to offer a little help in spreading the knowledge of low-incidence tumors in oncology, in order to alert the nonexpert clinician to take them into consideration, and to show the most accredited and updated medical treatment for some of the rare oncologic diseases. This booklet is not conclusive, but we hope to give help in prescribing treatments for the main RT, underlining the need of a multidisciplinary approach in these tumors, as well as cooperation with the centers of expertise. For the sake of brevity and competence, only solid RT are included; for the lymphoproliferative or hematologic low-incidence diseases we refer to hematologists. Each chapter provides brief information about the epidemiology of and clinical aspects for every RT; and, following each chemotherapy schedule, we report a short description of the hematologic toxicities related to the treatment.

Leseprobe

Chemotherapy regimens in rare solid tumors

Alessandro Comandone

Colophon

© SEEd srl

Piazza Carlo Emanuele II, 19 – 10123 Torino – Italy Tel. [phone] – Fax [email protected]

Chemotherapy regimens in rare solid tumors

Title of original Italian edition “Schemi chemioterapici e tossicità correlate” by A. Comandone, E.M. Berno, A. Boglione

First edition

September 2010

ISBN 978-88-9741-908-2

Although the information about medication given in this book has been carefully checked, the author and publisher accept no liability for the accuracy of this information. In every individual case the user must check such information by consulting the relevant literature.

This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the Italian Copyright Law in its current version, and permission for use must always be obtained from SEEd Medical Publishers Srl. Violations are liable to prosecution under the Italian Copyright Law.

Preface

Rare tumors (RT) are an increasing problem in oncology. A tumor is defined as “rare” if its incidence is ≤ 4 cases/100,000 people/year. Taken globally, such carcinomas are approximately 15–20% of all tumors, and represent a highly relevant health care problem.

The main characteristic of RT is the low frequency of the event, that determines difficult and sometimes late diagnosis and a great uncertainty in diagnosis and treatment. The expertise (i.e., knowledge about a specific RT and the number of cases managed in one year by a single clinician or group of clinicians) is the most important element for an adequate treatment of a patient with RT, together with a multidisciplinary approach. In fact, the occasional nature of the event, the scarcity of evidence-based proofs that can help diagnosis and therapy, and the lack of high-quality available medical literature expose the oncologist to the risk of diagnostic, prognostic, and therapeutic errors, especially if the information exchanged between the professionals involved is poor. As a consequence, the patient with RT often feels alone in facing the disease, because he/she does not find in other clinicians, especially if they are not part of a specialized center, the expertise and skills to manage the disease.

The most common results are, on the one hand, a forced migration of patients far from their residence in order to find doctors or centers of expertise, and on the other hand, a reliance on “miraculous treatments” of alternative medicine.

Moreover, RT can cause difficult problems in health care organization. Two very different organizational models can be found:

a concentration of cases in a few National Centers of Excellence, as happens in Scandinavian countries; and

a diffuse sharing of expertise in all hospitals, each authorized to treat patients with RT, as happens in the German model.

In the first model there is a risk of long waiting lists; in the second there is an increase of health care costs related to the proliferation of centers and the possible disparity of results between institutions with high expertise and general hospitals.

A better balanced model is the spread of the clinical knowledge in order to guarantee a good level of performance in early diagnosis and in first-level exams in general hospitals; while concentrating patients in referral institutes during the most complex periods, such as surgical intervention, therapies with innovative technology, or experimental medical treatments.

Since RT are neoplasms with different anatomic site of distribution, not a single expert is needed. For instance, pleural mesothelioma should be referred to a thoracic surgeon while a uterine sarcoma is a gynecological problem. So, the multidisciplinary team for every RT requests a complex organization to be realized in a wide geographical area.

Leading centers should be identified, in order to obtain from them support and learning, to diffuse the knowledge of these diseases, and to highlight the fundamental steps in diagnosis and therapy: this is the best way to assure the most adequate treatment to patients with RT.

This book cannot and does not try to offer solutions to all the problems related to RT; either it is not a simple handbook, making such a complex topic trivial. The aim is to offer a little help in spreading the knowledge of low-incidence tumors in oncology, in order to alert the nonexpert clinician to take them into consideration, and to show the most accredited and updated medical treatment for some of the rare oncologic diseases. This booklet is not conclusive, but we hope to give help in prescribing treatments for the main RT, underlining the need of a multidisciplinary approach in these tumors, as well as cooperation with the centers of expertise.

For the sake of brevity and competence, only solid RT are included; for the lymphoproliferative or hematologic low-incidence diseases we refer to hematologists. Each chapter provides brief information about the epidemiology of and clinical aspects for every RT; and, following each chemotherapy schedule, we report a short description of the hematologic toxicities related to the treatment. In this edition only the treatments approved by regulatory Agencies are reported, in order to avoid the off-label use, which is frequent and sometimes overused in RT. In few cases, we have indicated schedules and therapies not yet approved, but which are supported by strong literature evidence. These cases are specified.

We thank in advance all the readers who may assist us to improve the text giving us their advice and suggestions. We hope to be useful for everyday clinical practice.

Alessandro Comandone

Rare tumors of the thorax

Mesothelioma

Median incidence is 1.25/100,000 per year in Great Britain and 1.1/100,000 per year in Germany. The estimated incidence in high risk areas in Italy is 1.25/100,000 per year in males and 1.31/100,000 per year in females.

The incidence reaches a peak in the 55-70 age group and the number of cases is expected to double in 20 years.

About 70-80% of mesothelioma cases are estimated to be caused by asbestos exposure.

The most frequently affected sites are pleura (60-70%), peritoneum (30-35%), and pericardium (2%).

Diagnosis: early diagnosis is rare. Dyspnea, cough, chest pain, pleural effusion are the most common signs. Pleuroscopy is necessary for a histologic diagnosis.

Therapy: radical surgery is seldom applicable; the use of hemithoracic radiotherapy is limited; pleural talc insufflation is used as a palliative measure to control recurrent pleural effusion.

Survival in inoperable disease 10-12 months; 5-year survival 15%.

Mesothelioma: Cisplatin + Pemetrexed

Drug

Dosage

Schedule

Cisplatin

75 mg/m2 IV

Day 1

Pemetrexed

500 mg/m2 IV

Day 1

Every 21 days

Administer cisplatin 30 minutes after pemetrexed

Therapy to prevent toxicities: folic acid 350-1000 μg/day orally, starting 1 week before the first dose of chemotherapy; vitamin B12 1000 μg IM starting 1-3 weeks before the first dose of chemotherapy and repeated every 9 weeks while the patient is receiving the therapy. Premedication with corticosteroids (dexamethasone 4 mg twice daily): the day before and the day of the treatment.

Phase of the study

III

Number of patients

220

Response rate

41%

Complete response

0%

Vogelzang NJ et al. J Clin Oncol 2003; 21: 2636-44

Anemia

Grade 3 or 4 (6.4%)

Neutropenia

Grade 3 or 4 (34.6%)

Carteni G et al. Lung Cancer 2009; 64: 211-8

Mesothelioma: Carboplatin + Pemetrexed

Drug

Dosage

Schedule

Carboplatin

AUC 5 IV

Day 1; administered over 30 minutes

Pemetrexed

500 mg/m2 IV

Day 1; administered over 10 minutes

Repeat cycle every 3 weeks

Administer carboplatin 30 minutes after pemetrexed

Therapy to prevent toxicities: folic acid 350-1000 μg/day orally starting 1 week before the first dose of chemotherapy; vitamin B12 1000 μg IM starting 1-3 weeks before the first dose of chemotherapy and repeated every 9 weeks while the patient is receiving the therapy. Premedication with cortisone (dexamethasone 4 mg twice daily): the day before and the day of the treatment.

Phase of the study

II

Number of patients

102

Response rate

18.6%

Complete response

1.9%

Hughes A et al. J Clin Oncol 2002; 20: 3533-44

Ceresoli GL et al. J Clin Oncol 2006; 24: 1443-8

Anemia

Grade 3 or 4 (3.5%)

Neutropenia

Grade 3 or 4 (9.7%)

Ceresoli GL et al. J Clin Oncol 2006; 24: 1443-8

Mesothelioma: Cisplatin + Gemcitabine

Drug

Dosage

Schedule

Cisplatin

100 mg/m2 IV

Day 1

Gemcitabine

1000 mg/m2 IV

Days 1, 8, 15

Every 28 days

Phase of the study

II

Number of patients

21

Response rate

47%

Complete response

0%

Nowak AK et al. Br J Cancer 2002; 87: 491-6

Byrne MJ et al. J Clin Oncol 1999; 17: 25-30

Anemia

Grade 3 or 4 (24%)

Neutropenia

Grade 3 or 4 (61%)

Castagneto B et al. Am J Clin Oncol 2005; 28: 223-6

Mesothelioma: Cisplatin + Doxorubicin

Drug

Dosage

Schedule

Cisplatin

60 mg/m2 IV

Day 1

Doxorubicin

60 mg/m2 IV

Day 1

Every 21-28 days

Phase of the study

II

Number of patients

24

Response rate

25%

Complete response

0%

Ardizzoni A et al. Cancer 1991; 67: 2984-7

Anemia

Grade 3 or 4 (30%)

Thrombocytopenia

Grade 3 or 4 (24%)

Parra HS et al. Cancer 2001; 42: 650-6

Mesothelioma: Pemetrexed

Drug

Dosage

Schedule

Pemetrexed

500 mg/m2 IV

Day 1

Repeat cycle every 3 weeks

Therapy to prevent toxicities: folic acid 350-1000 μg/day orally starting 1 week before the first dose of chemotherapy; vitamin B12 1000 μg IM starting 1-3 weeks before the first dose of chemotherapy and repeated every 9 weeks while the patient is receiving the therapy. Premedication with cortisone (dexamethasone 4 mg twice daily): the day before and the day of the treatment.

Phase of the study

II

Number of patients

43

Response rate

16.2%

Complete response

0%

Manegold C. Semin Oncol 2003; 30: 32-36

Scagliotti GV et al. Export Opin Inverstig Drugs 2003; 12: 853-63

Anemia

Grade 3 (8%)

Neutropenia

Grade 3 (15%)

van den Bogaert DP et al. J Thorac Oncol 2006; 1: 25-30

Mesothelioma: Pemetrexed + Gemcitabine

Drug

Dosage

Schedule

Pemetrexed

500 mg/m2 IV

Day 8

Gemcitabine

1250 mg/m2 IV

Days 1 and 8

Every 21 days

Therapy to prevent toxicities: folic acid 350-1000 μg/day orally starting 1 week before the first dose of chemotherapy; vitamin B12 1000 μg IM starting 1-3 weeks before the first dose of chemotherapy and repeated every 9 weeks while the patient is receiving the therapy. Premedication with cortisone (dexamethasone 4 mg twice daily): the day before and the day of the treatment.

Phase of the study

II

Number of patients

52

Response rate

15%

Complete response

0%

Simon GR et al. J Clin Oncol 2008; 21: 3567-72

Jänne PA et al. J Clin Oncol 2008; 26: 1465-71

Anemia

Grade 3 or 4 (5.4%)

Neutropenia

Grade 4 (25%)

Jänne PA et al. J Clin Oncol 2008; 26: 1465-71

Mesothelioma: Gemcitabine + Cisplatin

Drug

Dosage

Schedule

Gemcitabine

1000 mg/m2 IV

Days 1, 8, 15

Cisplatin

70 mg/m2 IV

Day 2

Every 4 weeks

Phase of the study

Phase II

Number of patients

85

Response rate

44%

Complete response

0%

Giaccone G et al. Am J Clin Oncol 2006; 29: 336-44

Thrombocytopenia

Grade 3 or 4 (21%)

Neutropenia

Grade 3 or 4 (35%)

Lorusso V. Oncol Rep 2005; 13: 283-7

Thymoma

The incidence is 0.02 cases/100,000 per year and it represents 20% of all mediastinal tumors.

Age at diagnosis is between 50 and 60 years.

Diagnosis: occasional in 1/3 of the cases, consequent to compressive and infiltrative symptoms in 1/3 of the cases, consequent to myasthenia gravis in 30-50% of the cases.

Therapy: surgery is the recommended treatment; radical intervention leads to 5-year survival > 80%; adjuvant radiation therapy is recommended in patients with invasive forms who underwent resection with radical intent.

Thymoma: PAC

Drug

Dosage

Schedule

Cyclophosphamide

500 mg/m2 IV

Day 1

Doxorubicin

50 mg/m2 IV

Day 1

Cisplatin

50 mg/m2 IV over 1 hour

Day 1

Every 21 days

Phase of the study

II

Number of patients

22

Response rate

75%

Complete + partial response

63%

Loehrer PJ et al. J Clin Oncol 1994; 12: 1164-8

Kim ES et al. Lung Cancer 2004; 44: 369-79

Anemia

Grade 3 or 4 (57%)

Neutropenia

Grade 3 or 4 (93%)

Oshita F et al. Jpn J Clin Oncol 1995; 25: 208-12

Thymoma: PACE

Drug

Dosage

Schedule

Cyclophosphamide

800 mg/m2 IV

Day 1

Doxorubicin

45 mg/m2 IV

Day 1

Cisplatin

80 mg/m2 IV

Day 1

Etoposide

80 mg/m2

Days 1 → 3

G-CSF

90 mg/m2

Days 5 → 18

Every 21 days

Phase of the study

II

Number of patients

30

Complete response + CP

50%

Oshita F et al. Jpn J Clin Oncol 1995; 25: 208-12

Loehrer PJ et al. J Clin Oncol 1994; 12: 1164-8

Anemia

Grade 3 or 4 (57%)

Neutropenia

Grade 3 or 4 (93%)

Oshita F et al. Jpn J Clin Oncol 1995; 25: 208-12

Thymoma: ADOC

Drug

Dosage

Schedule

Cisplatin

50 mg/m2 IV

Day 1

Doxorubicin

40 mg/m2 IV

Day 1

Vincristine

0,6 mg/m2 IV

Day 3

Cyclophosphamide

700 mg/m2 IV

Day 4

Every 21 days

Phase of the study

II

Number of patients

8

Response rate

75%

Fornasiero A et al. Cancer 1991; 68: 30-3

Koizumi T et al. Am J Clin Oncol 2002; 25: 266-8

Anemia

Grade 3 or 4 (50%)

Neutropenia

Grade 3 or 4 (12.5%)

Berruti A et al. Br J Cancer 1999; 81: 841-5